Friday, 31 March 2017

The Ghost Aim in Medical Research – A Subjective Limit in Intake to Prevent Fattening/Insulin Resistance/Overall Inflammation

The division had a start when I read the Handbook of Physiology of the American Society for Physiology, in 1967. I was charged with the treatment of malnutrition and diarrhoea in the University of Florence. I read the handbook to become aware about mucosal digestion and absorption. At that time, these points had to be diagnosed to treat malnourished children. Before beginning any research, I intended to adapt intake to intestinal physiology. I read that 50% - 60% or more immune cells of the human body reside in the mucosa of small intestine (Mowat, 1987, 44; Brandtzaeg et al., 1989; Abrams, 1977). Bacteria grow in small and large intestine by slow energy production without oxygen use. All fibers and small amounts of sugars, carbohydrates, proteins, fats escape intestinal digestion and provide energy for one bacterial replication per day (Hungate, 1967). 

Food avoided absorption due either to excessive intake or to incapability to be digested. Fibers like cellulose and pectin escape digestion and promote slow growth of poorly immunogenic bacteria species and prevent harmful microbiome developments. Bacterial growth becomes immunogenic and harmful when energy dense food is largely available. In the mammal intestine, bacterial indiscriminate, harmful growth is proportionate to a positive energy balance in blood and in body. Thus I studied bacteria number on intestinal mucosa in time after last meal. A longer interval from the meal produced a decrease in bacteria number. An increase in mucosal and overall immune stimulation is associated with bacteria growth on intestinal mucosa, with preprandial blood glucose (BG) and with a slowdown of meal absorption (Ciampolini et al., 1996; 2000). Energy balance directly affects these correlated variables either increasing or lowering the conflict between bacteria activity and mucosal immune response. The initial hunger meal pattern (IHMP) was devised to reduce bacterial growth and reduce the mucosal.

immune response at nutrient absorption. This conflictual state between bacteria and mucosa has been confirmed (Cooper, Siadaty, 2014; Mccoy, Köller, 2015). The many successful cures of gastrointestinal pathologies suggest that the conflictual theory that was used for recovery was objective, i.e. reproduced the events in small and large intestine. In this view, the question:” what food provokes cancer?” is absurd. Malignancy needs to be surveilled and prevented through an increase in efficiency of immune system (Kristensen, 2017). Lower intestinal stimulation may be the way to achieve higher immune efficiency also in the body (Abrams, 1977; Brandtzaeg et al, 1989; Ciampolini et al, 1996; Kubes, Meahl, 2012; Lynch, Pedersen, 2016). 

Thus health(general immune efficiency) follows the relation between energy intake and expenditure. Hundreds or thousands of bacterial species live and multiply in the intestine, 5% - 15% of the species elicit IgG production, the intestinal mucosa responds with an immune reaction and, lastly, the immune stimulation by bacterial antigens spreads of to all body tissues (Overall Subclinical Inflammation). Thus, many observations sustain the conflictual view for the absorption of every energy dense food. Unfortunately, a different, confounding opinion may be repeated by a high number of researchers and become the dominant view. Now, hundreds of scientific Journals ask me for submitting articles. I am alone and cannot produce hundred articles that are new and different each other to repeat the statements about the conflictual absorption and the IHMP solution for health maintenance and recovery. Yet, the upsurge of malignant and vascular risks, not to mention malnutrition that affects one billion of malnourished people, impose to spread the awareness on this “ghost aim”.  

Thursday, 30 March 2017

Atrial Fibrillation: A Theoretical Assumption and a New Perspective

The most common cardiac arrhythmia in clinical practice is atrial fibrillation (AF). The cause for the development of AF has been investigated by many studies, however, the question remains unanswered. A recently published hypothesis suggested that atrial fibrillation is a physiological mechanism, of protective value, based on the discontinuation of atrial mechanical systole. This lowers the pressure within the system of the pulmonary veins and alveolar capillaries, in pathological situations, and as a result reduces the probability for development of pulmonary congestion and edema. This hypothesis explains the connection between left ventricle (LV) dysfunction and AF, helps with designing algorithms of relationships between AF and LV dysfunction, and with various diseases and conditions, suggests a new approach to the location of the source of AF and shows a protective function of the atriums in the development of LV dysfunction. There is a correlation between this hypothesis and the known facts and phenomenons associated with AF.

It is known that the most common arrhythmia in clinical practice is atrial fibrillation (AF) and is very often associated with LV dysfunction / heart failure (HF). It is called the epidemic of the century. An arrhythmia that is particulary common in the elderly, AF is growing in prevalence with the ageing of the population. In addition to age, there are many types of cardiac and medical conditions that are also closely linked to AF. These include hypertention, coronary artery disease, heart failure, valvular heart diseases, hyperthyroidism and so on. Despite the fact that there have been many studies carried out on the subject of “AF-a cause or consequence?”, the question remains unanswered.

In the years 2015-2016 the new hypothesis was proposed, which assumes that AF is a protective physiological mechanism in the cases of LV dysfunction/heart failure and it answers many questions related to the AF. The reasoning of the hypothesis is as follows. The end diastolic pressure (EDP) is the algebraic sum of the left ventricle diastolic pressure (LVdp) and left atrial systolic pressure (atrial kick pressure, AKp). EDP=LVdp+AKP. Normal range of EDP is 8-12 mm Hg, AKp is 2-6 mm Hg. At the end of the diastole when the mitral valve(MV) is still open, EDP immediately transmitted and equalized (according to hydrodynamic law) throughout the communicating system of the LV, LA, pulmonary veins(PV), and alveolar capillaries(AC), as there are no obstacles to the spread of the EDP wave. EDP is thus equal to pulmonary wedge pressure (PWP) with a normal range of 8-12 mm Hg. In the conditions of LV dysfunction (HF varying degrees), EDP increases due to failure of the LV (i.e. LV diastolic pressure component increases). EDP = LVsp + AKp. This increased EDP at the end of diastole with opened MV transmits to the entire communicating system of the LA-PV-AC and with the increased PWP, but with the threat of exit of fluid through the alveolar-capillary membrane. When PWP increases to 20 mm Hg, pulmonary edema is usually present.

Wednesday, 29 March 2017

The CT and MRI Findings of Fibrinous Sialodochitis

Fibrinous sialodochitis is a very rare disease in which the recurrent swelling of the salivary gland is caused by the obstruction of the glandular duct by a fibrinous material. Few studies have reported both the computed tomography (CT) and magnetic resonance imaging (MRI) findings of fibrinous sialodochitis. We reported a forty-nine-year-old man with this disease including CT and MRI findings. His chief complaint was the recurrent swelling of the bilateral submandibular regions. When his primary dentist pushed them strongly, a whitish jelly-like material and a large amount of clear saliva were expelled from the duct orifices of the submandibular glands. A CT and MRI findings showed the retention of saliva in the glandular duct and no abnormal sign of the glandular parts. On a cytological examination, the material included fibrinous substances and numerous eosinophils. According to clinical, radiological and cytological findings, the patient was diagnosed with fibrinous sialodochitis. The management included the massage to compress the salivary glands, the administration of antihistamines and steroids, and irrigation of the ducts of submandibular glands using a saline solution. The number of times of the swelling of the submandibular regions decreased.

Fibrinous sialodochitis is a very rare disease. It is characterized by the recurrent swelling of the salivary gland, which is caused by the obstruction of the duct by a fibrinous material. When the salivary glands are compressed, a fibrinous material is expressed from the duct orifice, and the swelling disappears. To our knowledge, there were only sixteen case reports about fibrinous sialodochitis in the English literature. However, few studies have reported both the computed tomography (CT) and magnetic resonance imaging (MRI) findings of fibrinous sialodochitis. We herein present a case of fibrinous sialodochitis and report the CT and MRI findings.

A forty nine-year-old man was referred for the evaluation and treatment of recurrent swelling in the submandibular region from a general dental clinic to Osaka University Dental Hospital. His chief complaint was the recurrent swelling of the bilateral submandibular region over a one-year period. He did not have pain or fever. His medical and family histories were unremarkable. 

Tuesday, 28 March 2017

The Gynecologyst and the Family Doctor as Lawyers

Obstetricians and Gynecologists manage to solve problems of health of the woman in state of pregnancy, puerperium and lactation as well as the physiological and clinical pathological states proper to its sex. They treat the diseases related to the genital apparatus of the woman benign or malignant and the alterations that compromise its functional state. They also provide care to women with ethics and a critical spirit that allows them to rationalize diagnostic methods for the study of their problems. The gynocologist proposes adequate guidelines for the therapeutic management of the problem at the collective or individual level. On the other hand, family doctors are the first point of entry for health-care delivery, with links to higher levels of the health system and other services. Family physicians do not treat diseases but take care of people. Family medicine is the medical specialty which provides continuing, comprehensive health care for the individual and family within the context of community. Providing family-oriented primary care is one of the distinguishing features of this specialty. 

Gynecologists and family doctors are the two medical specialties that fundamentally share medical care for health problems and preventive actions in women. In this field, both have to work as a team. And they share the difficulties of managing women’s health problems. Both also have to face a major risk: overdiagnosis and overtreatment. Although this phenomenon occurs in all medical specialties, women take better care of their health, and they rely more on prevention than men, so it is not surprising that they are more affected by the excess of all types of health activities; the “excess medicine”.The clinical work is involved in the uncertainty because the application of the Truths of biomedical science in the life and in the circumstances of each individual patient will always be uncertain. So doctors, especially young doctors, are learning to fear to the uncertainty. We are asking for more and more evidence. To try to assure ourselves, often in vain, of what we are seeing. And because we are afraid that those who are in the kingdom of the healthy, perhaps should be in the realm of the sick, continually divert resources from the sick to the healthy, and so the overdiagnosis is inevitably linked to the insufficient treatment of those who are already sick. Overdiagnosis of the healthy and insufficient treatment of the sick are two sides of the coin of modern medicine.

 In this context, it can be logical that the concepts and theories that belonging to Interface between gynecology and family medicine are often difficult to explain and to understand. To show this interface, with an educational approach, we can do it through metaphors. Metaphors enable us to understand something that is unknown in terms of its familiarity. For this reason, they are used frequently in all sciences that adopt common words to name complex realities. The metaphors are analogue devices, used to illuminate reality. Metaphors can simplify expert knowledge, not by ignoring or reducing the inherent complexity, but by providing a point of entry for its comprehension. They are a means of generating ideas, promoting creativity, and constructing concepts and theories. Thinking based on metaphors and comparisons is a way of transforming a concept into something that is so suggestive, interesting, and surprising, that it reaches people more easily.

Monday, 27 March 2017

Role of QRS Complex Fragmentation in Patients at High Risk of Cardiovascular Events


The presence of fragmented QRS complexes (FQRS) on a routine 12-lead ECG is an interesting marker of depolarization abnormality. There is convincing data suggesting that the FQRS represents conduction delay from inhomogeneous activation of the ventricles due to myocardial scar. However, FQRS is not specific for coronary artery disease and is also encountered in other myocardial diseases such as cardiomyopathy and congenital heart disease. FQRS has also been described in other entities such as arrhythmogenic right ventricular cardiomyopathy and Brugada syndrome. 

The significance and the predictive value of FQRS complex as an ECG marker of cardiovascular events seem to be different in different entities. In patients with stable coronary artery disease and in patients with acute MI, FQRS seems to be a good predictor of cardiac events. In patients with non-ischemic cardiomyopathy, fragmentation of narrow QRS complex seems to correlate with the degree of fibrosis and dys-synchrony, and importantly may influence the response for cardiac resynchronization therapy. However, based on clinical studies with larger number of patients with current indications for cardiac resynchronization, FQRS does not influence and is not associated with poor response of resynchronization therapy. In patients with LV dysfunction, there is no clear evidence that the presence of FQRS could predict arrhythmic events. On the other hand, there was a statistical significant difference in mortality associated to the presence of fragmented QRS in patients with acute coronary syndrome and myocardial necrosis.

Invasive and non-invasive tests for risk stratification of cardiovascular events were studied in the context of coronary artery disease, cardiomyopathy and heart failure. One of the recent non-invasive tests, microwave T-wave alternans and signal-averaged electrocardiogram have high negative predictive values but have a low positive predictive value in patients with history of myocardial infarction (MI) or cardiomyopathy. A low left ventricular ejection fraction in patients with structural heart disease is used routinely in clinical practice for risk stratification with a major limitation being the lack of desirable positive predictive value for the risk of cardiovascular events. The presence of fragmented QRS complexes (FQRS) on a routine 12-lead ECG is another marker of depolarization abnormality. There is convincing data suggesting that the FQRS represents conduction delay from inhomogeneous activation of the ventricles due to myocardial scar. However, FQRS is not specific for coronary artery disease and is also encountered in other myocardial diseases such as cardiomyopathy and congenital heart disease. FQRS has also been described in other entities such as arrhythmogenic right ventricular cardiomyopathy and Brugada syndrome. In 1969, Flowers et al. named high-frequency components to the presence of fragmented QRS (FQRS) complexes. 

Friday, 24 March 2017

Open Dialogue-a Contribution to a Healthier World: Threat or Chance?

In this article the dilemma of psychiatry as a medical science is outlined as well as options, where we as psychiatrists should turn to. Open Dialogue as a therapeutic approach to severe mental health crisis is introduced and described in its principles and elements. A case description illustrates how principles and elements are set to work. Connections to the upcoming Peer Movement are drawn as well as to EU-Legislation about Deinstitutionalisation and the UN-Convention of Civil Rights for People with Disabilities (UN-CRPD). Finally the difficulties in implementing such a comprehensive approach are outlined to get closer to an answer, whether this kind of change has more of a chance or tends to be a threat.

Since a couple of years it is obvious, that psychiatry as a science is facing a fatal crisis, but resistance to acknowledge some facts, that showed up, is strong within the profession, and that for many reasons. Still like in the middle ages the ambassadors of the new knowledge get kind of “burnt” on the bonfires of certain journals, as if to kill the messenger who brings in bad news. It looks like some facts are too disturbing to have a closer look at them. And we don’t have to name it a “Copernican Turn” what is happening, it is more that we gathered knowledge that does not fit the mainstream assumptions in psychiatry. In this I follow Pat Bracken, Bob Whitaker  and Peter Gøtzsche as well as some others, who have been dealing with different aspects (Joanna Moncrieff [5], Volkmar Aderhold, Stefan Priebe and P. Bracken  sum up what we gained through what is called scientific research in the last decades and it is very sobering to imagine the billions of Euros spent. What for? Yes, as much as nothing. They could not lift any secrets of the brain as much as to be helpful for our patients. 

The same is true forbrain imaging techniques and genetics. Robert Whitaker has had a closer look at the longterm outcome of different kinds of studies concerning different kinds of psychiatric treatment and comes to the conclusion that following the guidelines of medical – pharmacological treatment as usual leads to an outcome worse, than we would have expected and those patients who manage not to fall into the desired “compliance” and refuse to take long term medication, have better chances to recover and be included in more sufficient working and living conditions. He also revealed the way that business interests of the psychiatric profession and big pharma met in a fatal way for the benefit of the two, unluckily it turned out to be a disadvantage for the patients. He also revealed through epedemiological data in western countries a fourfold rise of disability allowances for mental health problems and connects it to the dominant treatment system. Peter Gøtzsche as head of the Northern European Cochrane Association investigated the scientific background of the admission of certain substances to the market and revealed criminal power behind it. Joanna Moncrieff managed to show, that theories about a chemical imbalance in the brain in the case of mental illness is nothing but a fairy tale, just a seemingly plausible invention. Stefan Priebe as a socially oriented psychiatrist has become the “mockingbird” of Psychiatry. He writes about the missing results of the investments in research over the last decades and its meaninglessness for the therapeutic endeavors. So we work in a mental health system that is built on wrong assumptions, produces more problems than it can solve, is more devoted to money and its implications than to those citizens, who are facing severe crisis and thus getting dependend on support. What a mess, we might say, and yes, it is. But the situation is far from being hopeless. 

Luckily we know a lot about how we could improve our attempts to offer help, that can be not only accepted but also helpful!! By now, we know from the experiences in the Soteria Movement,(Mosher Ciompi the results from longterm studies(Huber, Ciompi und Müller, Vermont Study, Harrows, Wunderinck, West- Lappland)the acknowledgement of human wisdom through philosophy, Buber  Bateson  Developmental Psychology (Trevarthen Stern [18] Reflective Processes and Open Dialogue (J. Seikkula, T. E. Arnkil enough to know, in which direction we should go. science made the race and we have to admit, they had and still have fantastic results in medicine as well as other disciplines. But then there came up the idea to apply this approach of looking at smaller and smaller parts of living organisms as human beings, first brain architecture, than nerves, followed by research on cells and synaptic connections, now on an intracellular level of mitochondria or membranes. 

Thursday, 23 March 2017

Acid-Coagulated Cheese Making by Streptococcus Thermophilus and Lactobacillus Delbrueckii Subsp. Bulgaricus Fermetation as a Helpful Technology


Acid coagulated cheese plays an important role in the food of peoples living in the areas or counties with large amount of fresh milk production. The quality and safety could not be guaranteed by the present traditional processing technologies with natural fermentation. In the present study, five different kinds of lactobacteria mixtures were used as the starters of the acid coagulated cheese. To determine better starter, the effects of the five groups of starters were compared and then the processing parameters of the cheese were optimized. The starter consists of two kind of Streptococcus thermophilus (SP1.1:TM11) and Lactobacillus delbrueckii subsp. bulgaricus (34.5) with a mass ration of starter powders of SP1.1 and TM11 to 34.5 is 90: 10: 1, which was proved to be the best starter mixtures. The cheese made according to the optimal processing parameters, starter addition 0.003%, fermentation temperature 40o C, CaCl2 0.03% and the appropriate cutting time is 0.5 h when the pH value of whey reached 4.6, showed better properities. These results will provide some fundamental data to promote the industrialization process of the traditional acid coagulated cheese with manufactured lactobacterial starters.

Acid coagulated cheese is a kind of fresh cheese and well known for its smooth texture, sour taste and distinctive flavor. Different from enzyme coagulated cheese, the curdling of milk in acid coagulated cheese relies on the acid produced by lactobateria or the addiction of edible acid. Acid coagulated cheese is a traditional food in many minorities in China or many areas famous for raw milk production, including the milk lump in Xinjiang Kazakhs, the milk tofu in Mongolia, Qula in Tibet, the milk cake in Yunnan Yi and the dairy fan in Yunnan Bai. Acid coagulated cheese is about 25% percent of the total amount of the global cheese products, which indicates its important role in the cheese industry. Also, acid coagulated cheese will be well developed due to its simple process, low-intensity labor, low costs and high production efficiency. However, in the traditional process, the acid coagulated cheese will be naturally fermented. The bacteria compositions in atmosphere in different areas are varied significantly, the processing technology varied in tools and container, temperature, processing parameters, etc, in different scale household workshop, and these conditions contribute to the varied product qualities, especially on the aspects of flavor, taste, texture and shelf life. 

In this present study, the optional compound strains for acid coagulated cheese making was determined from five different compound lactic acid bacteria, and the optional processing parameters were investigated by designing orthogonal experiments, which provides theoretical directions for large-scale industrial production. 

Wednesday, 22 March 2017

Case Report the Muscle Loss in the Intra Operative Strabismus Surgery

A lost muscle is one of the most devastating complications that a strabismus surgeon can face in the intra-operative period. Rectus muscles can be lost due to trauma or surgery, including sinus surgery, strabismus surgery, and other ocular surgeries. A lost medial rectus muscle is usually expected in the presence of an overcorrection after exotropia surgery or under correction after exotropia (XT) surgery, resulting in limited duction in the field of action of the muscle. If not treated, a lost muscle will lead to consecutive strabismus, diplopia, and a large limitation of eye movement in the direction of the lost muscle.

A 31 years old man, native of Sao Luis, was referred to the strabismus service due to XT complaints ever since the age of 10, in addition low vision in the right eye. On ophthalmological examination was verified best-corrected visual acuity 0.05/1.0; with preference for the left eye. Concerning extrinsic eye muscles presented XT 25^ concomitant. On monocular rotation tests we found +2 right lateral rectus with ametropic in both eyes. Bio microscopy and funduscopy unaltered in both eyes. The surgical plan was 6.0 mm right medial rectus (MR) resection and a 5.0 mm withdrawal of the right lateral rectus. Due to its friability and lack of support for suturing, the right MR muscle was lost during surgery. Therefore, a transposition of superior rectus to the MR was performed, using a technique similar to that of Jensen’s. The post-operative results after a month were XT 40 (on Hirschberg test) and -2 right medial rectus on monocular rotation tests, besides of normal bio microscopy and funduscopic evaluations (Figure 1).

Upon six months of post-operative, the patient presented concomitant XT 25^ and 12 of right hypertropia (on Krimsky test) and -2 right MR on monocular rotation. One year after the first surgery, a second approach was done with the initial plan being. It was receded right lateral rectus 12.0mm plus 1.0mm anterior dislocation of the right lower oblique ahead of the right inferior rectus (peribulbar). However, due to the increased risk of anterior chamber ischemia, a triple marginal myotomy was performed on the right lateral rectus including anterior dislocation right lower oblique (1.0mm ahead of the right inferior rectus edge) and innervation (recede of the left lateral rectus 8.0 mm). On the seventh post-operative day, the patient presented XT 12^ with right hypertropia 10^, monocular rotation tests showed -2 and -3 right MR and -2 right lateral rectus. Three months after the second intervention, the patient displayed good healing, right hypertropia 15ˆ, and -2 right lateral rectus and -2 right MR (Figure 2), monocular rotation tests with the patient now being discharged.

Monday, 20 March 2017

Antimicrobial Efficacy of Callus and in Vitro Leaf Extracts of Sapindus Mukorossi Gaertn. Against Pathogenic Microbes

Sapindus mukorossi is well known medicinal and economical plant. Antibacterial and antifungal activities were evaluated from various extracts (ethanolic, methanolic and aqueous) of callus and in vitro leaf against several Gram positive and Gram negative bacteria and clinically isolated fungus. Antimicrobial activities were more in in vitro leaf extracts. Callus extract have showed antibacterial activity against S. aureus and E. coli. Maximum inhibition zone (8.06±0.17 mm) was observed against C. tropicalis from methanolic extracts of in vitro leaf. In vitro leaf extracts have shown efficient antifungal activity. Callus and in vitro leaf extract can be used for production of different phytochemicals and plant based antibiotics.

Plants are rich source of secondary metabolites and have great therapeutic potential to treat various diseases. A large population of world uses plant based principles for their primary health care. Medicinal plants may be proved as best source of a variety of drugs. About 20% of plants present in the world have been examined for pharmaceuticals and biological tests. The commonly present antibiotics are either derived from natural or synthetic resources. Several researchers have reported the various biological activities such as antimicrobial, anti-inflammatory, anti-HIV, anti-cancer, antidiabetic etc. from different group of plants. Current research shows that researchers and medical professionals are more interested in the use of indigenous drugs for the cure of human health ailments. Due to expensiveness and more side effects of synthetic drugs clinical microbiologists are paying their attention for screening of medicinal plants for phytochemicals and antimicrobial activity as potent therapeutics.

Antimicrobial activities of medicinal plants are due to presence of different groups of phytochemicals such as alkaloids, polyphenolic compounds, terpenoids, lignans etc. Human pathogens are developing drug resistance against commonly used antibiotics have compelled researchers for searching new antimicrobial substances from other natural sources including plants. So, there is an essential need to develop a new generation of antibiotics from natural source. S. mukorossi Gaertn. is a popular medicinal and economical tree and well-known for their therapeutic values. S. mukorossi plant is rich in antioxidants and polyphenolic compounds and exhibiting antioxidants properties. Earlier, Aneja et al. have assessed the antibacterial activity of fruit extract against dental caries causing pathogen. Antimicrobial activities of leaf and fruit extracts of this plant were also evaluated on some bacteria and fungus. For the validation of antimicrobial potential of this plant this research study was undertaken. This is the first report of antimicrobial activity by using callus and in vitro leaf (IVL) extracts.

Leaves of S. mukorossi were collected from the campus of Banaras Hindu University, Varanasi, in the month of April. Callus and IVL were regenerated by following the protocol of Singh et al. Callus was shade dried at room temperature for 4-5 days and at 40-45°C for 2 h and grinded in mechanical grinder to make coarse powder. Five gram of callus powder was extracted in 150 ml of solvents for 10 h using Soxhlet apparatus. Ethanol, methanol and double distilled water were used as solvents for the extraction. Extracts were then dried at 40°C in rotary evaporator and stored at -20°C for further use. Test samples were prepared in different concentrations for further experiments in their respective extraction solvents. In vitro leaf (200 mg) was collected and grinded in mortar and pestle by adding the solvents. Finally, volume of extract was maintained about 20 ml.

Friday, 17 March 2017

The Rapid and Sensitive Hplc-Ms/Ms-Method of Determination of Mebeverine Metabolites in Human Plasma

The rapid and sensitive method for quantifying mebeverine metabolites in human plasma was developed using HPLC-MS/ MS. Mebeverine acid-D5 and desmethyl mebeverine acid-D5 were used as internal standards. Sample preparation was performed by protein precipitation. The chromatographic separation was achieved on Phenomenex Luna C8 Mercury (20 x 4.0 mm, 5 μm) and Phenomenex Luna 5u C8 (150 x 4.6 mm, 5 μm) under gradient conditions of mobile phase. The calibration range of mebeverine acid and desmethyl mebeverine acid was 10 – 2000 ng/ml. The method was applied to conduct a pharmacokinetic study of 200 mg prolonged-release capsules Duspatalin on 24 healthy participants.

Mebeverine is myotropic antispasmodic agent which effect is based on blockade of fast sodium channels and slow calcium channels on membrane of myocytes. It slows down depolarization of the membrane and prevents contraction of muscle fibers. The drug has high selectivity to smooth muscles of the gastrointestinal tract. Therefore it is primarily used to relieve spasms of organs of the digestive system. Mebeverine being an ester is rapidly hydrolyzed in step of first-pass elimination by esterases to 3.4-dimethoxybenzoic (veratric) acid and mebeverine alcohol. The main metabolites of the drug are mebeverine acid (MA) and desmethyl mebeverine acid.

The half-life of DMA after administration of prolonged-release capsules of mebeverine is 5-6 h, maximum concentration in blood (Cmax) after a single dose is 679 ng/ml, after repeated doses 804 ng/ml, time-to-peak concentration (Tmax) is about 2.92 hours. The area under the curve “concentrationtime” from last blood sampling procedure (AUC0-t) for DMA is 4552 ng∙h/mL, the elimination constant is 0.147. The values of pharmacokinetic parameters for MA were not published. Therefore, obtaining new data about pharmacokinetic of mebevere in the form of prolonged-release capsule is actual. Several analytical methods of quantitative determination of mebeverine metabolites in plasma using HPLC and HPLC-MS/ MS were reported. However, these methods have some disadvantages, such as necessity of complex sample preparation, using solid-phase and liquid-liquid extraction, and lack of sensitivity (high LLOQ).  

Thursday, 16 March 2017

HIV/AIDS: The Past, Present and Future

Human immune deficiency virus (HIV) is closely related to the simian immunodeficiency virus which is found in monkeys and apes. HIV-I is closely related to the strains of SIV found in chimpanzees, and HIV-II is closely related to the strains of SIV found in the sooty mangabeys. In 1999 some scientists found a strain of SIV ( called SIVcpz) in chimpanzees that was closely related to HIV-I in humans. It was then concluded that this proved that chimpanzees were the source of HIV-I and had crossed species to humans at some point in time. Furthermore it was thought that these chimpanzees got the SIV virus by eating two smaller monkeys (red-capped mangabeys and greater spot nosed monkeys) and became infected with two strains of SIV. These two strains joined together to form the SIVcpz strain which has the ability to infect humans. This was followed by the concept of the hunter who ate these chimpanzees and became infected or the viruses were able to access the hunter through wounds and cuts. Ocassionally the hunter would be able to ‘fight’ off this SIV, but sometimes they were able to survive in humans as HIV. 

HIV-II comes from SIVsmm in sooty mangabey monkeys rather than chimpanzees. The crossover to humans is believed to have happened in a similar way (through the killing and consumption of monkey meat). It is far rarer, and less infectious than HIV-1. As a result, it infects far fewer people, and is mainly found in a few countries in West Africa like Mali, Mauritania, Nigeria and Sierra Leone. There are four groups of HIV strains M,N,O,P with M being the most common with nine subtypes (A-D,F-H,J,K). There are so many strains because in the attempt to enter and adapt to survive within the human system the SIV had to evolve into several strains the most successful being able to survive the new environment.

Researchers have come to the conclusion that this “zoonotic” infection of humans with this virus started around 1920 in the Democratic Republic of Congo. The same area is known for having the most genetic diversity in HIV strains than anywhere else, reflecting the number of different times SIV was passed to humans. Many of the first cases of AIDS were recorded there too. The extensive transport routes in that part including the railways, rivers and road networks together with the high migrant population and growing sex trade all supported the spread of the HIV virus. The lack of transport routes in the north and east of the country accounted for the lower reports of infections from these regions at the time. By 1980, half of all infections in DR Congo were in locations outside of the Kinshasa area, reflecting the growing epidemic. 

Wednesday, 15 March 2017

Bilateral Stress Fractures of Pubic Ramus in a Patient affected by Hyperparathyroidism


This case report presents a 48-year-old patient who was diagnosed of bilateral pubic ramus stres fracture in one year period. She was admitted with hip and groin pain. In our case, direct radiography followed by MRI was used for diagnosis. Hyperparathyroidism was detected as a etiological cause. Patient underwent conservative treatment for bilateral stres fractures of pubic ramus with perfect results. Attending to this case report, in patients with non-traumatic groin pain and endocrinological disorders, pubic ramus stress fracture is a diagnosis that should be kept in mind.

Stress fractures are those that occur in a local area of a normal or pathologic bone, due to less powerful forces that will normally result in a complete fracture. This kind of fractures are divided into three different subgroups: fatigue fracture, insufficiency fracture, and pathologic fracture. Fatigue fractures occur in healthy bones due to unusual mechanical effect. Their prevalency is increased in young adults, especially in weight bearing bones. Attending to the risk factors, fatigue fractures are most frequenly observed in athletes, dancers, and soldiers. On the other hand, insufficiency fractures occurs as a result of reduced bone resistance under normal bearing. Many clinical risk factors have been identified with this fracture type, including osteoporosis, osteomalacia, hyperparathyroidism, rheumatoid arthritis, long term use of cortisone, diabetes mellitus, fibrous dysplasia, renal insufficiency, and radiotherapy.

Attending to insufficiency fractures, most pelvic insufficiency fractures occur in women, particularly those with osteoporotic bone. They represent, approximately, 1-2% of all the stress fractures, and they most commonly observed at the pubic ramus. This kind of fractures are usually asymptomatic; nevertheless, these patients ay present groin and back pain. For our knowledge, bilateral pubic ramus stress fracture due to hyperparathyroidism has not been reported previously. In this case report, we present a case report of a female patient affected of this type of fracture and realize a short review about of stress fractures in patients affected of endocrinological mineral balance disorders, including hyperparathyroidism. 

Tuesday, 14 March 2017

Pregnancy Outcomes Upon Using Arabin Pessary in Cases of Premature Cervical Shortening


Spontaneous preterm birth is the leading cause of perinatal morbidity and mortality. Several methods were found to be helpful in preventing preterm deliveries in singleton gestations. Those include progesterone administration and different cervical cerclage. Arabin Pessary which is a silicone made device has been explored in recent years as a method of preterm birth prevention. In contrast to singleton gestations, neither progesterone administration nor cervical cerclage were found to be affective in a multi-gestational pregnancy. Our article describes three cases with increased chances of preterm delivery. Two singletons and one multi-gestational pregnancy. All three women received a cervical Arabin Pessary in addition to the accepted treatment of progesterone. All three women had favorable results and delivered healthy infants. We concluded from our experience and from trials conducted in centers around the world that cervical Arabin Pessary is beneficial in preventing preterm birth both in singleton and in multi-gestational pregnancies.

A 40 year old gravida 5 para 1, turned up for a medical evaluation 23+6 weeks gestation after in vitro fertilization [IVF] due to lower abdominal pressure. Primary evaluation determined 20 millimeters cervical length with a U shaped funneling. Her history included a genetic screening which demonstrated 2% 45 x0, 4% 47xxx and 94% 46 xx genetic mosaicism. During her previous pregnancy she experienced cervical shortening at 16 weeks gestation. McDonald’s cerclage was administered. At 25 weeks gestation cesarean section was performed after she experienced septic shock and the cerclage was removed. Her first trimester genetic screening determined a 1:95 chance for down’s syndrome. Second trimester genetic screening determined a 1:170 chance for down’s syndrome. She refused to go throw amniocentesis. 200 mg of Uterogestan®( Laboratoires Besins International) was given once daily and Arabin Pessary was inserted upon the cervix. During her admission period she was diagnosed with gestational diabetes mellitus which was well controlled with a low carbohydrate diet was discharged at 27 weeks gestation and returned to labor and delivery in active labor 36+4 weeks gestation. She delivered vaginally. The fetus weighed 2400 gram and received Apgar scores of 9 and 10 after 1 and 5 minutes.

A 25 year old gravida 1 para 0 bichorionic biamniotic twin pregnancy after intrauterine insemination[IUI] turned for a medical evaluation 25 weeks gestation due to uterine contractions. Her medical history is within normal limits and so does her first and second trimester genetic screenings. Her cervical length was 23 mm dilated to 3 cm [figure 1]. In addition, the amniotic sac was exposed at the external cervical os. Her Monitor exhibited recurrent contractions. After Atosiban®[Ferring] administration contractions have subsided. She received magnesium for neuroprotection and Celestone. Arabin pessary was installed upon the cervix . 

Friday, 10 March 2017

A Brief Overview of Post-Partum Obsessive Compulsive Disorder

General postpartum mood disorders, specifically depression and anxiety, have been well studied in the literature. However, there is limited data regarding the identification, diagnosis, and management of postpartum obsessive compulsive disorder (ppOCD). Women with this diagnosis are frequently undiagnosed or misdiagnosed and, regretfully, suffer with their symptomatology. The purpose of this review is to educate the clinician on the prevalence and signs and symptoms of ppOCD, and to offer recommendations regarding the pharmacologic and psychotherapeutic management of this disorder.

Postpartum OCD is thought to occur in approximately 1-5% of all postpartum mothers. Pregnant and postpartum women are more likely to experience OCD compared to the general population. Risk factors include a personal history of anxiety disorders and/or OCD, personal history of depression (El-Mallakh or a family history of anxiety or depression. The onset of symptoms may occur rapidly, within a week of delivery. Interestingly, the focus of the obsessions and compulsions are similar between mothers. Aggressive obsessive thoughts involving the baby are significantly more common in groups of women with postpartum depression. Due to the disturbing obsessive thoughts that mothers have, many fear telling their physician or families for concern that their child will be taken from them, resulting in non-identification and non-treatment of their disorder.

As part of a routine postpartum follow up exam, the Edinburgh Postnatal Depression Scale (EPDS) is recommended for evaluating women for postpartum depression. This scale includes 10 questions which are completed by the patient and scored by the provider. Within this scale, some questions (#4- 6) focus on anxiety symptoms. If and when women have elevated scores on this section, it is worthwhile to further investigate for anxiety disorders, including ppOCD. Although there is no specific screening tool for ppOCD, the Florida Obsessive Compulsive Index (FOCI) is one example of a screening tool that can be given to the postpartum patient for completion. Scores of 8 or higher on this scale are highly suggestive of OCD. For providers that may not have access to the EPDS or FOCI, simply asking the woman if she finds herself having repetitive thoughts or avoiding certain things or behaviors may give the clinician additional information and evidence for a diagnosis of ppOCD. This should lead the clinician to further investigate the symptoms and determine whether they need additional evaluation by the clinician or referral to a psychiatrist. 

Thursday, 9 March 2017

More Folic Acid in Pregnancy May Protect Kids From High Blood Pressure


Higher folic corrosive levels amid pregnancy may diminish the danger of hypertension in kids if their moms have coronary illness hazard considers, another review suggests."Our think about includes additional proof the early life starting points of hypertension," said senior relating creator Dr. Xiaobin Wang, a pediatrician from Boston University. "Our discoveries raise the likelihood that early hazard evaluation and intercession before origination and amid pregnancy may prompt to better approaches to avoid hypertension and its outcomes crosswise over life expectancy and eras," Wang said in a diary news discharge. 

She and her exploration partners took a gander at information from right around 1,300 mother-youngster sets from births at Boston Medical Center. The mothers and children were taken after from 2003 to 2014. 66% of this gathering were dark, and about 20 percent were Hispanic.The scientists needed to check whether a lady's folic corrosive levels and coronary illness chance components - including hypertension, diabetes and heftiness amid pregnancy independently and mutually affected a kid's blood pressure.Nearly 29 percent of the kids had hoisted systolic pulse from ages 3 to 9 years. Systolic pulse is the top number in a circulatory strain perusing. Kids with higher pulse will probably have moms with pre-pregnancy weight, hypertension and diabetes. 

Those youngsters were additionally more prone to have bring down birth weight, bring down gestational age and a higher body mass list (BMI - a gauge of muscle to fat quotients in light of tallness and weight). More elevated amounts of folic corrosive amid pregnancy were related with a 40 percent bring down danger of hypertension among offspring of moms with coronary illness chance variables. 

Notwithstanding, a mother's folic corrosive levels alone were not connected with a youngster's pulse. She needed to likewise have coronary illness chance elements for folic corrosive to have any kind of effect, the review found.

Wednesday, 8 March 2017

Have Americans Given Up on Losing Weight?


Americans are overweight or fat, however many have abandoned attempting to lose those overabundance pounds, another review appears. 

One in each three individuals in the United States is presently corpulent, contrasted and one in five 20 years prior, scientists report. 

In any case, individuals overviewed in the vicinity of 2009 and 2014 were 17 percent more outlandish generally speaking to state they'd attempted to get more fit amid the earlier year than those reviewed in the vicinity of 1988 and 1994, the review found. 

Individuals who were overweight however not yet fat have encountered the best loss of enthusiasm for keeping up a solid weight, said senior specialist Dr. Jian Zhang. 

"This is bad. We are feeling the loss of the chance to prevent overweight from getting to be weight," said Zhang, who is a connect teacher of the study of disease transmission with Georgia Southern University. 

Zhang and his associates dissected information from the U.S. National Health and Nutrition Examination Survey, a governmentally subsidized continuous study that monitors Americans' wellbeing and eating routine propensities. 

All racial/ethnic gatherings crosswise over both sexual orientations detailed diminished enthusiasm for weight loos,but ladies specifically will probably say they'd abandoned it, the discoveries appeared. 

By 2014, dark ladies were 31 percent less inclined to have attempted to get more fit contrasted and two decades earlier, and white ladies were 27 percent less inclined to have made the endeavor, the specialists found. 

Individuals may abandon weight reduction since it's recently excessively troublesome, Zhang said. 

"It's excruciating," he clarified. "It's difficult to drop pounds. A significant number of us attempted and fizzled, attempted and fizzled, lastly neglected to attempt any longer." 

Current drug additionally has become better at safeguarding the general wellbeing of overweight individuals, maybe making them inquire as to why they ought to trouble, Zhang proceeded.

Tuesday, 7 March 2017

New Nasal Spray, Noctiva, Reduces Nighttime Urination


A nasal shower definition of desmopressin acetic acid derivation, successful at lessening the quantity of times grown-ups need to urinate amid the night, has been endorsed by the U.S. Sustenance and Drug Administration. 

Noctiva (desmopressin acetic acid derivation) is a nasal splash for grown-ups who make no less than two evening treks to the washroom because of causes, for example, certain prescriptions, perpetual heart disappointment inadequately controlled diabets and bladder and prostate issues, the Associated Press reported.The shower, utilized around 30 minutes before sleep time every night, helps the kidneys ingest more water keeping in mind the end goal to diminish the measure of pee. 

Noctiva conveys a discovery cautioning - the FDA's most grounded - about the danger of hazardously low levels of sodium in the blood. Other conceivable symptoms incorporate colds, bronchitis, an ascent in circulatory strain, unsteadiness, back torment and nose drains, the AP detailed.