Thiamine and the cellular energy cycles: a novel perspective on type 2 diabetes treatment

None of the currently available therapeutic interventions for type 2 diabetes mellitus address the intracellular metabolism of glucose through the main energy pathways of the cell. Thiamine [vitamin B1] is a water-soluble vitamin and essential normal dietary component. When modified in the body to the pyrophosphate derivative, it acts as a coenzyme for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and transketolase which are required for the utilization and consumption of glycolytic and hexose monophosphate pathway intermediates and form an integral part of intracellular and glucose metabolism. Thiamine deficiency decreases the activities of these enzymes, leading to imbalances in the metabolic pathways. The effects of these imbalances are more pronounced in diabetes mellitus where renal dysfunction produces mild thiamine deficiency. This indepth review presents a novel perspective on, the cellular energy cycles, thiamine dependant enzymes, pharmacotherapeutics of type 2 diabetes especially thiamine and their impact on type 2 diabetes treatment. Thiamine, with its well established safety record, easy accessibility and affordability could be an invaluable adjunct for our type 2 diabetic population and help to improve the quality of their lives by giving them some respite from the complications of type 2 diabetes and perhaps reduce the need of more expensive oral hypoglycaemic agents required by them

Lunate dislocation

Carpal dislocations are wrist injuries and Lunate dislocation is its severe form. Lunate and perilunate dislocations are uncommon. These injuries have significant clinical impact on the patient but are easily missed and lead to potentially devastating effect if mismanaged. This case report outlines the important clinical aspects and management of Lunate dislocation

Evaluation of anti-inflammatory activity of isolated flavonoids from mucuna pruriens seeds

Modern day medical science is still waiting for more potent and safer drugs and anti-inflammatory drugs are no exception

Purpose of the study: Seeds of Mucuna pruriens have shown to possess anti-inflammatory activity and we planned to test flavonoids and alkaloids to find the active principles because both of them are found in relatively higher concentration in seeds of Mucuna pruriens plant

Materials and Methods: Study has been carried out in four groups of eight albino mice each, group I [control], group II [standard], group III [flavonoids] and group IV [alkaloids]. Carrageenan induced paw edema has been used to evaluate the anti-inflammatory activity by recording the edema development after 1-, 2-, 3-, and 4- hours after Carrageen an injection in the right dorsal surface of hind paw of mice

Results: Flavonoids have shown significant anti-inflammatory activity with p <0.05 after 1-, 3- and 4 hours whereas they have mild activity at 2 hours [P < 0.05]

Conclusion: Isolated flavonoids from Mucuna pruriens seeds have showed significant anti-inflammatory activity whereas alkaloids have not shown any significant anti-inflammatory activity. So, flavonoids are most likely responsible for the anti-inflammatory effect of Mucuna pruriens

Evaluation of analgesic activity of isolated flavonoids from mucuna pruriens seeds

Medicinal plants have been used as analgesics since millennia

Purpose of the study: Seeds of Mucuna pruriens have shown to possess analgesic activity and we planned to test flavonoids and alkaloids to find the active principles because both of them are found in relatively higher concentration in seeds of Mucuna pruriens plants

Materials and Methods: This study has been carried out in four groups of eight albino mice each, group I [control], group II [standard], group III [flavonoids] and group IV [alkaloids]. Formalin paw licking test has been used to evaluate the analgesic activity by recording the number of lickings for 30 minutes after formalin injection in dorsal surface of left hind paw

Results: Flavonoids have shown significant analgesic activity [mean no. of lickings 24.25 +/- 8.97] p<0.05. While alkaloids have not shown any significant analgesic activity [mean number of lickings 39 +/- 6.78]

Conclusion: Isolated flavonoids from Mucuna pruriens seeds have showed significant analgesic activity whereas alkaloids have not shown any significant analgesic activity. So, flavonoids are responsible for the analgesic effect of Mucuna pruriens

High dose thiamine intervention for non traditional risk factors in type 2 diabetic angiopathies

Background: Impaired fibrinolysis, prothrombotic states, altered second messenger signaling mechanisms and enhanced oxidative stress levels have all been termed as the nontraditional risk factors of micro and macrovascular disease in diabetes mellitus. These are significant promoters of the pathogenesis of diabetes in general and type 2 diabetes in particular. High dose Vitamin B1 [thiamine] has been found at preclinical level to play an ameliorative role through a number of intracellular metabolic pathways. In order to demonstrate whether this was translatable to a clinical therapeutic level in type 2 diabetics, pioneering research on the effect of high dose thiamine on associated markers of incipient diabetic nephropathy, hemostasis [plasminogen activation inhibitor 1PAI1], oxidative stress [plasma thiols] and seond messenger signaling [protein kinase C] was conducted

Methodology: 100 Type 2 microalbuminuric type 2 diabetics were enrolled in a randomized, double blind placebo controlled clinical trial for 6 months. Patients were divided into two groups, one was orally administered 300 mg/day thiamine, while the other group was provided placebo for a period of 3 months followed by a 2 month washout period. 50 normal healthy controls participated bar baseline estimations only. Plasma and urinary thiamine levels, microalbuminuria, metabolic, plasminogen activation inhibitor 1 [PAI1], oxidative stress marker plasma thiols and second messenger signaling protein kinase C profile was determined in normal controls at exclusively baseline. While in type 2 diabetics the same profiling was performed at baseline, 3 months post therapy and 2 months post washout, using HPLC flourimetric detection for thiamine, estimation kits for protein kinase C, plasminogen activation inhibitor, glycated hemoglobin, microalbuminuria and specialized assay protocol for plasma thiol determination

Results: Markedly lower median plasma thiamine concentration of diabetic patients [7.5 nM] was present compared to normal range of normal healthy human subjets [44.6-93.7 nM.]. Thiamine treatment for 3 months increased median plasma thiamine concentration 10 fold and urinary thiamine excretion 29 fold. It reduced significantly, microalbuminuria by 33% and glycated haemoglobin by 1.4%. Type 2 diabetics had significantly higher plasminogen activation inhibitor type 1 and protein kinase C levels at baseline, +82.5% [p<0.000] and 3.56 fold [p<0.001] respectively as compared to normal controls. Following 3 months thiamine therapy, plasminogen activation inhibitor type 1 levels remained unchanged, while levels of protein kinase C were reduced significantly by 555 in thiamine treated diabetics and this decrease was maintained at a lowered rate of 44% even 2 months after discontinuing the drug [p<0.01]. While the placebo group in comparison registered a significant increase of 26.09% in protein kinase C levels [p<0.05] which persisted during the washout period. Oxidative stress marker, plasma thiols was reduced significantly by 21% in diabetics at baseline versus normal controls with no change occurring following thiamine or placebo therapy as well as after washout

Conclusion: Type 2 diabetics were microalbuminuric, thiamine depleted with deranged metabolic, fibrinolysis, second messenger signaling and oxidative stress profile as compared to the normal population. High dose thiamine therapy significantly improved micoalbuminuria, glycated haemoglobin, thiamine status and decreased protein kinase C levels with no significant impact on oxidative stress and fibrinolysis profile

Evaluation of anti-inflammatory activity of Mucuna pruriens Linn. Seeds

Inflammation is associated with pathophysiology of various clinical conditions like arthritis, gout and cancer. Numbers of drugs are being used to treat inflammation but they are partly effective and have significant adverse effect profile. Mucuna, pruriens is traditionally used to relieve fever, pain and inflammation

Purpose of the study: to evaluate the anti-inflammatory activity of Mucuna pruriens Linn. seed powder

Materials and Methods: this study has been carried out in five groups of albino mice, having eight animals each. Three different doses of Mucuna pruriens Linn seed powder has been given to three groups and anti-inflammatory activity has been compared with the other two groups, standard and control Carrageenan-induced paw edema has been used to evaluate the anti-inflammatory activity and decrease in paw edema after 1-, 2-, 3-, and 4-hours have been interpreted as anti-inflammatory activity

Results: mucuna pruriens Linn seed powder showed significant anti-inflammatory activity in all three groups as depicted by decrease in edema after 1-, 2-, 3-, and 4-hours [p < 0.05]

Conclusion: mucuna pruriens seed powder showed significant anti-inflammatory activity in all three groups of mice and activity increases with increasing the dose of seed Powder

Diabetes mellitus: its epidemiology and pathogenesis: a global focus on type 2

Diabetes mellitus enjoys pandemic status. Majority of patients will suffer, life threatening complications resulting from microvascular and macrovascular damage associated with diabetic nephropathy, cardiovascular and cerebrovascular disease, dyslipidemias and a plethora of intracellular and extracellular biochemical abnormalities. New theories regarding its pathogenesis and specially those for type 2 have emerged over the years. This review focuses on the different aspects of epidemiology, pathogenesis and presentations of type 2 diabetes mellitus

Assessment of body mass index [BMI] in medical students [a cross sectional survey]

Obesity is nutritional imbalance and it is under the influence of environmental and genetic factors, increase in high-energy intake and a reduction in physical activity. All overweight and obese are at risk for hypertension, high blood cholesterol, type 2 diabetes, coronary heart disease, etc. Unfortunately obesity is increasing in modern world and this is reported by many researchers. This rising magnitude of the problem mandates population-level intervention. For which a quality data is needed. This study was conducted to fill this knowledge gap for designing a suitable preventive strategy. To know the etiological factors in the area, to formulate a public awareness and intervention programme for reduction in mortality and morbidity due to obesity in Pakistan. Cross-sectional survey. KEMU June to July 2006. Pre-tested questionnaire was used to interview the 4[th] yr MBBS students. Although obesity is present in some students but, surprisingly the percentage of students who were under weight was more than the over weight/obese. Obesity is significantly more in economically well students, whereas under wt. students belong to all the economical classes. Economical prosperity and sedentary life style are the most important suspected causes of obesity where as low wt. trend was either due to fashion of looking smart of due some awareness. Awareness programme are the best feasible approaches for rectification of the situation for neither being over- weight nor under wt

Assessment of severity of cirrhosis in hospitalized patients

Background: To assess the severity of cirrhosis at the time of presentation to hospital and to seek association between sociocultural, demographic and geographic variables and severity of chronic liver disease

Materials and Methods: One hundred consecutive cases of cirrhosis of liver admitted in Nishtar Hospital, Multan were included in this study. After history, physical examination and relevant investigations, patients were segregated into Child grade A, B and C depending upon the severity of liver disease

Results: Among 100 cases studied, 48 were male and 52 female; the mean age was 47 years [range 20 to 80 years]. Majority of the patients were from low socio economic group. Out of 100 cases 72% were from rural areas and 28% were from urban areas. It was found that most of the patients [92%] presented to hospital when their liver disease was advanced [46 patients of Child grade B and 46 patients of Child grade C] while only 8 patients had mild liver disease [Child Grade A]. Rural population had more severe disease at the time of presentation as compared to urban population. Poor and middle socioeconomic group had more severe and advanced chronic liver disease as compared to rich class [p=0.0306]. It was found that female had more severe disease at the time of presentation [P=0.0346]. Frequency of cirrhosis was found to be more above 40 years of age

Conclusion: Results of this study indicated that cases of cirrhosis of liver are referred to tertiary care units when their disease is advanced with serious complications. Moreover there is a significant association between geographic and socioeconomic status of the patients and severity of cirrhosis. It is recommended that health care personnel should be properly trained for health education and early recognition and referral of the patients of chronic liver disease to tertiary care units. This will prevent complications and with help to decrease the morbidity and mortality

Clinical study of rheum emodi, ammonium chloride and potassium nittrate in drug induced hepatotoxicity of tubercular patients

A number of anti-tubercular drugs are used for the treatment of tuberculosis for a long duration of time. Most common drug combination for the short course chemotherapy is Rifampicin, Pyrazinamide, Isoniazid, and Ethambutol. In the long-term therapy, these drugs cause hepatotoxicity due to their adverse effects i.e. hepatitis, hepatic insufficiency, cholestatic hepatitis and fulminant hepatitis. Several Unani drugs have been reported as hepatoprotective agents, such as kasni, afsantin, zafran, nagar motha, gul-e-ghafis, naushader, shora qalmi, revand chini etc. In the present research work a powdered formulation containing revand chini [Rheum emodi], naushader [Ammonium chloride] and shora qalmi [Potassium nitrate] was prepared and studied clinically along with the anti-tubercular drugs during the first month of the treatment of tuberculosis in male and female subjects. The blood samples of the patients were collected before and after treatment and estimated for liver function tests i.e. serum bilirubin, serum glutamic pyruvic transaminase [SGPT] and serum alkaline phosphates [SAP]. The patients were also observed for subjective/symptomatic parameters e.g. nausea and vomiting, loss of appetite, constipation, flatulence and hepatomegaly. Hepatomegaly was examined by the physician and other parameters were recorded in the follow-up. Significant hepatoprotective effects were observed in both male and female subjects, although more prominent effects were observed in female subjects. The other symptoms such as nausea, vomiting, loss of appetite, constipation, flatulence and hepatomegaly were reduced in the ATT+Unani treatment groups as compared with anti-tuberculosis treatment alone. In conclusion, the Unani formulation along with the anti-tubercular drug treatment was found beneficial in reducing the side effects of anti-tubercular drugs on liver of the patients

Leech in the hypopharynx: an unusual cause of bleeding from throat

Combined Military Hospital, Peshawar and Army Medical College, Rawalpindi. This paper presents as a case of a 22 year-old young man who presented with a 4-day history of bleeding from throat. Indirect laryngoscopy revealed a blackish living foreign body in the right laryngo-pharynx. Pharyngo-laryngoscopy under general anaesthesia showed a leech, which was removed by forceps. We conclude that a high index of suspicion of leech infestation is required when faced with bleeding from throat

Combined liver and kidney transplant for a pa patient with primary hyperoxaluria: 11 years Follow-up

We report a 30 year-old male who developed end - stage renal disease at the age of 12 years due to primary hyperoxaluria. After six months of heamodialysis he received a cadaver kidney transplant. Five years later the allograft failed because of heavy oxalate deposition. After three months of heamodialysis he received combined liver and kidney transplant with the immunosuppression of Tacrolimus and prednisone. Now after 11 years of follow up he has normal liver functions, stable renal function with serum creatinine around 200 micro mol/L and normal daily urine oxalate excretion. This case illustrates the long-term success of combined liver-kidney transplantation for treatment of primary hyperoxaluria with renal failure

Spina bifida occulta: the common radiological finding in lumbosacral spine radiograph with low backache below forty years

OBJECTIVE: To find out the common radiological findings in lumbosacral spine radiograph of patient with low backache below forty years. DESIGN: Prospective study of 241 patients complaining of low backache visiting Radiology Department for Lumbosacral Spine X-ray. SETTING: Department of Radiology, Memon Charitable Hospital, Hyderababd. PERIOD: January 1997 to April 1997 MAIN OUTCOME: Spina Bifida Occulta, is the most common radiological finding in lumbosacral spine x-ray, below 40 years with low backache. RESULT: 159 cases from 241 patients sent for lumbosacral spine x-ray AP view shows SBO. 78 were male and 81 were female. 59.1% show SBO in S1 segment. Mean age group was between 21-30 years in female, and 31-39 years in male. Associated lesion was also present apart from spina bifida occulta. The most common were Cutaneous Dimple 45.20%, followed by Lipoma 22.01%. CONCLUSIONS: SBO was found to be the most common radiological finding in AP view of lumbosacral spine x-ray below forty years, due to lack of public health awareness, and folic acid deficiency, during the antenatal period of their mother

Application of polymerase chain reaction to detect rearrangement of immunoglobulin heavy chain genes in lymphoproliferative disease

As part of our routine work-up in the diagnosis of lymphoproliferative disease, we used a rapid polymerase chain reaction [PCR] assay to amplify the DNA fragments of the framework 3 [FR3] region of the immunoglobulin heavy [IgH] chain genes. The assay does not involve hybridization, nested priming, or sequencing of the amplified PCR product. It was performed on 66 specimens of B-cell lymphoproliferative disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, hairy cell leukemia and follicular lymphoma. Twenty-six specimens of negative controls, including acute myeloid leukemia, chronic myeloid leukemia in myeloid transformation and idiopathic thrombocytopenic purpura, were also analyzed. The assay was performed with 77% sensitivity and 100% specificity. The standard IgH chain gene rearrangement by Southern blot analysis is reserved for the remaining negative cases if clinically indicated

Clinical evaluation of the efficacy and safety of piroxicam gel [05] in the treatment of acute musculoskeletal disorders

The purpose of this study was to evaluate the efficacy and safety of Piroxicam gel [0.5%] in the management of acute well defined sprains and tendinitis. Forty patients completed the study. One gram Piroxicam gel [0.5%] was applied 3-4 times daily up to a period of maximum 14 days. Twenty-seven [67.5%] were suffering from Distorsio pedis [sprained ankle], 10 [25%] were suffering from epicondylitis [tennis elbow], 2 [5%] patients were suffering from Achilles Tendinitis and 1[2.5%] patients was suffering from Tendinitis M. supraspinatis. Patients showed improvement in all efficacy parameters assessed which included symptomatology, pain on active movement at affected site, and the ability of the patient to accomplish a chosen activity. At the end of the treatment period, 22 [55%] patients had no pain on movement, while the pain score dropped to 2.22 from average baseline score of 15.07. Twenty-four [60%] patients had no tenderness and 11 [27.5%] had very slight tenderness at the end of the treatment. Out of 36 patients who had restriction of movement at baseline, 25 [69.4%] had no restriction of movement at the end of treatment. The ability to accomplish a chosen activity returned to normal in 29 [80.5%] patients out of 36 who had chosen an activity at the beginning of the treatment. In patients self assessment and investigators' assessment, the overall efficacy was rated as excellent to good in 26 [65%] and fair in 12 [30%] and poor in 2 [5%]. Overall tolerance was excellent to good in 36 [90%] and fair in 4 [10%]. No side effect was either reported by any patient or observed by the investigator in this study

Spent bullet injuries in the head and neck region

There is increasing incidence of various injuries caused by wandering spent bullets. These injuries have been encountered in Head and Neck regions, upper limbs and trunk. They can cause severe morbidity and can prove to be fatal. Many such cases have not been reported in literature. There are two reports available in literature, one from Jordan by Hanieh and other from Peshawar [Pakistan] by Rafiq Khan et al. We report an other case of the same nature

Rare lethal midline granuloma of the nasopharynx Stewards's granuloma

We report a case of lethal midline Granuloma of the Nasopharynx. Lethal midline Granuloma of the nose is a rare tumor and its occurrence in the Nasopharynx is still more rare