Hepatitis B virus subgenotype A1 predominates in liver disease patients from Kerala,India

AIM:To molecularly characterize hepatitis B virus(HBV)isolates from Kerala and to relate them to the clinical manifestation of infection.METHODS:Sera and clinical data were collected from91 patients diagnosed with chronic HBV infection and HBV-related hepatocellular carcinoma(HCC).HBV from44 HCC,22 cirrhotic and 25 chronic hepatitis patients were genotyped by sequencing of the complete S region or by restriction fragment length polymorphism assays.The basic core promoter/precore region was sequenced.The complete surface DNA sequences were assembled and aligned manually,and then compared with the sequences of HBV of genotypes(A-J)from GenBank.The evolutionary history was inferred using the Neighbor-Joining method and the evolutionary distances computed using the Kimura 2-parameter method.Bootstrapping was performed using 1000 replicates.The TaqMan BS-1 probe was used to quantify HBV DNA at a lower detection limit of approximately20 IU/mL.Continuous variables were compared using an independent Student’s t test.Theχ2test or Fisher’s exact test was used to compare categorical variables.The differences were considered statistically significant at P<0.05.RESULTS:Irrespective of disease status,the predominant genotype was A(72%);95%belonging to subgenotype A1,followed by genotypes D(27%)and C(1%).HCC patients infected with subgenotype A1were significantly younger than those infected with D.Mutation A1762T/G1764A was significantly associated with HCC in both genotypes A and D.Mutation G1862T was more frequent in subgenotype A1(P<0.0001),and in combination with A1762T/G1764A,it was significantly associated with HBV from HCC patients.Mutation C1766T/T1768A was significantly associated with genotype A(P=0.05)and HCC(P=0.03).The preS2start codon M1T/I mutation was unique to genotype A strains(15.6%)from all disease groups and occurred at a higher frequency in isolates from HCC patients(P=0.076).A higher frequency of preS deletion mutants(33.3%)was observed in genotype A from HCC compared with non-HCC patients,but     

Diabetes and driving

More than 69 million Indians are suffering from diabetes, of which a substantial proportion of the population are currently holding or will seek in the future the license to drive. Driving essentially requires multitasking with visuospatial skills at the same time and thus the management of diabetes in individuals which should demonstrate a proper detection and treatment of diabetes-related hypoglycemia will predict the capacity of driving any motor vehicle. Repeated hypoglycemia-related neuroglycopenia causes increased risk of neurocognitive dysfunction leading to visuospatial skills deficiency. Eight percent of dementia may be attributed to diabetes. Potential causes of driving impairment associated with diabetes are acute hypoglycemia, and its unawareness, retinopathy, neuropathy related to foot that affects ability to use pedals, IHD, cerebrovascular disease, somnolence and sleep disorder associated with obesity, use of pain relieving medications and antidepressant, and cognitive dysfunction and thus should be reviewed properly before issuing a driving license. Medical evaluation and documentation of acute and chronic complications of drivers by a registered medical practitioner at pre-determined intervals may be considered as a legal necessity to identify at-risk drivers. Secretagogues have a higher incidence of hypoglycemia compared to someone who is on metformin alone. On the other hand, hypoglycemia is more frequent in an insulin-treated patient of both type 1 and type 2 diabetes. In many countries as well as in European Union (EU), it is necessary to review medical fitness in every 3 years by the authority; a person should not have any severe hypoglycemic event in preceding 12 months and a driver must have awareness of hypoglycemia and its management. According to Canadian diabetes association consensus statement, review should be done every 2 years; a person should not have any severe hypoglycemic event in preceding 6 months, and according to ADA position statement evaluation should be done every 2–5 years. Medical fitness certificate should be reviewed at frequent intervals; the authorities should enforce strict regulation on suspension and revocation of driving license. Information to the authorities should be promptly done by doctors or patients. Decision should be based on medical evaluation, but hypoglycemia that occurs due to medication change and during sleep does not warrant for disqualification as it may be corrected with proper dietary changes and dose adjustments. Any driver with suspended license should be re-assessed in the next 6 months for their medical fitness and hypoglycemic profile and if found suitable, the license can be revoked. Physicians should participate and should assess patient’s physical and mental status, medical condition and treatment, list of medications which may impair driving performance, and any disease-related complication that lead to impaired driving or dangerous driving. Patient education is the most important factor to prevent any motor accident related to their medical condition and should be trained to prevent acute and chronic complications of diabetes.     

Developing ultra deformable vesicular transportation of a bioactive alkaloid in pursuit of vitiligo therapy

ObjectiveTo develop transfersomal formulation integrated with piperine intended for vitiligo.MethodsFilm hydration technique was employed in the preparation of transfersomes. Modified diffusion cell, consistency tester were fabricated for ex vivo diffusion studies and spreadability studies respectively while tape stripping method was integrated with tissue extraction in the determination of tissue drug concentration.ResultsWhen film hydration technique was used for, ultradeformable vesicles (transfersomes) of piperine in soabean phosphatidylcholine was formed with (67.11±0.22) to (70.55±3.62) and (60.12±1.04) to (80.43±0.14) mean size (μ) and entrapment efficiency (%) respectively. Transfersomes are capable of crossing the pores in permeability barriers extremely efficient even if the transfersome radius (t_r) is much greater than the pore size (r_pore) ie., tr/r_pore? 0.25 the driven flux rate depends on the transdermal osmotic gradient. The vesicles describes elasto-mechanical character of vesicles while penetrating through the pores. The proviso is that the vesicular membrane elasticity is dynamically to the local stress by the external. Diffusion and Spreadability studies showed maximum diffusion when the lipid was kept minimum. Tape stripping and tissue extraction method for the tissue drug retention showed that (75.25±1.72)% drug was retained in the dermis.ConclusionSpan 80 was preferred over tween 80 in terms of dermal retention. Size and encapsulation was slightly altered by phosphatidylcholine concentration. The kinetics, efficiency and the transfersome mediated transport can be tailored for trans-epidermal, deep tissues and systemic depending on the vesicular composition, dose and form. Thus we have offered a successful drug delivery of piperine targeting the deep epidermis.     

In ova angiogenesis analgesic and anti inflammatory potency of Aerva Monsoniae (Amaranthaceae)

ObjectiveTo evaluate the wound healing potency of aqueous extract of Aerva monsoniae (A. monsoniae) by in vitro method using fertilized eggs, in vivo analgesic and anti inflammatory activity in rodents and the anti bacterial activity on the bacterial strains that infect the wound.MethodsThe whole plant of A. monsoniae was extracted with water and then subjected to preliminary chemical screening. It was then evaluated for in ova angiogenesis on fertilized white leg horn eggs using the concentrations of 200-600 μ g/mL. The analgesic activity was evaluated in mice using the dose 100 and 250 mg/kg. The anti inflammatory activity was evaluated in rats using the dose 250 mg/kg and 500 mg/kg. In both the parameters water was used as the control and diclofenac was used the standard. The anti bacterial activity on Staphylococcus aureus and Pseudomonas aerugenosa was performed.ResultsThe phytochemical screening revealed the presence of tannins, flavonoids and saponins. The in ova angiogenesis revealed a dose dependent activity which proves the wound healing claim of the plant as more number of blood capillaries were formed at the site of the drug. The plant proved to be a potent analgesic and anti inflammatory agent at doses 100 mg/kg and 250 mg/kg. The anti bacterial activity was present but at higher doses.ConclusionsThe parameters studied in the present investigation proved that the plant is a potent wound healer. Further in vivo wound healing studies on animal model is desired. As the extract showed potent analgesic, anti inflammatory and anti bacterial properties, it can be considered that when formulated into suitable formulation, and it can reduce the pain, inflammation and infections related to wound very well.     

Growth in Children with Steroid Sensitive Nephrotic Syndrome

Background

Nephrotic syndrome in children usually has an onset between 2-8 years of age and steroids form the mainstay of management. Therapy may affect growth in children with relapsing nephrotic syndrome. This study was carried out to correlate growth with the cumulative dose of steroids in children with steroid sensitive nephrotic syndrome (SSNS).

Methods

Data of 35 children with SSNS was analysed retrospectively. They were divided into two groups. Group I received prednisolone only and Group II received levamisole and or cyclophosphamide in addition to steroids. Their heights were recorded at the time of inclusion and again one year later. The SD scores for age were determined. Growth rate as a change in the SD score over one year (Δ SD score) was correlated to the cumulative dose of steroids over the same period using the Pearson''s correlation. Result: There were 24 (68.6 %) boys and 11 (31.4 %) girls (M:F ratio 2.18:1) in the age group of 17 months to 11 years at inclusion. Group I constituted 19 (54.2 %) and Group II, 16 (45.8 %). Pearson''s correlation coefficients for all children, Groups I and II were -0.341, -0.441 and -0.255 respectively indicating “Fair correlation”. This indicates that as the cumulative dose of steroid increases the growth retardation becomes more apparent.

Conclusion

Growth retardation is proportional to the cumulative dose of steroids in children with SSNS.Key Words: Steroids, Cumulative dose, Nephrotic syndrome, Growth