Evaluation of Effect of Ascorbic Acid on Ferritin and Erythropoietin Resistance in Patients of Chronic Kidney Disease.

OBJECTIVE: This study was planned to evaluate the effect of short term intravenous ascorbic acid on reducing ferritin and erythropoietin resistance in patients of chronic kidney disease (CKD) on maintenance haemodialysis (MHD). METHODS: Forty adult patients [20 patients in group A with increased serum ferritin level (>500 ng/ml), transferrin saturation (TSAT) ≤20% and 20 patients in group B with normal serum ferritin level (<200 ng/ml), TSAT ≤20%] of end stage renal disease (ESRD) with erythropoietin hyporesponsiveness undergoing maintenance hemodialysis were included in the study. Group A was given intravenous (i.v.) ascorbic acid in a dose of 500 mg once a week after each 4 hours session of dialysis for 3 weeks in a month (total 1500 mg/month), for a period of 3 months along with erythropoietin 6000 IU subcutaneous (S/C) twice weekly without iron therapy. Group B was given erythropoietin (6000 IU S/C twice weekly after each hemodialysis) and intravenous (IV) iron 100 mg/week for 3 months. Hematological and renal investigations, erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (HsCRP), serum ferritin and TSAT were done at baseline and then one monthly intervals for three months whereas intact parathyroid hormone (iPTH) was measured at the start and end of the study. RESULTS: At the end of 3 months of study, in group A, Hemoglobin (Hb) and TSAT significantly increased while ferritin, HsCRP and erythropoietin resistance index (ERI) decreased significantly. In group B, the increase in Hb and TSAT were not significant statistically while ferritin increased significantly and fall in HsCRP and ERI were not significant statistically. The mean rise in Hb between subsequent months was higher in group A as compared to group B. CONCLUSIONS: Short term i.v ascorbic acid could be a new successful adjuvant in reducing ferritin and erythropoietin resistance and enhancing Hb and TSAT in CKD patients on MHD.

Role of ACE and IL-1ß Gene Polymorphisms in Erythropoeitin Hyporesponsive Patients with Chronic Kidney Disease with Anemia.

BACKGROUND: Hyporesponse to erythropoietin is a common problem seen in around 5-10% of patients. Recently the focus from these remediable factors has been shifted to the non-modifiable innate factors i.e polymorphism of ACE and IL-1B gene and studies have shown that DD genotype and IL-1B CC genotype have lower erythropoietin requirement. The aim of our study was to evaluate the role of ACE and IL-1B gene polymorphisms in erythropoietin hyporesponse in CKD patients with anemia. METHODS: A total of 50 patients were selected. After taking pre-informed written consent, they were segregated into two groups, group A and B with 25 patients in each group. Group A included CKD stage III-IV patients and Group B included CKD stage V patients who were on regular maintenance. All patients were given erythroepoietin and response was monitored using erythropoietin resistance index (ERI). Genotyping of ACE and IL-1B genes were done and serum levels of ACE and IL-1B were measured. Mean values of ERI were compared between different genotype subgroups and analysed using binary regression analysis. RESULTS: The study group included 6 patients with diabetic nephropathy and out of these 4(66.6%) had DD genotype. On comparing the effect of ACE polymorphism on ERI levels it was seen that the mean ERI values in DD subgroup were significantly lower (16.97±5.35, 21.88±6.25, 22.69±8.35 at 1,3 and 5th month) as compared to ID (18.16±3.39, 24.17±3.66, 32.74±9.95 and II (20.73±5.17, 27.74±7.30, 41.08±13.83 U/Kg/g/dL). In the case of IL-1B the mean ERI values were lowest in the TT subgroup (16.46±4.45, 21.96±5.77,23.98±8.48) as compared to CC (19.49 ±5.62,25.46±7.07, 33.59±12.61) and CT (18.12±4.27,24.14±5.70, 31.89±13.83 U/Kg/g/dL). The mean serum values of ACE were in a decreasing trend i.e DD> ID> II (238.05 ± 52.46, 194.73±50.28 and 162.99±39.71 ng/ml, (p < 0.05). The mean serum values of IL1B in CC, CT and TT were 23.24±28.77, 18.32±16.25, 23.34±13.83 pg/ml (p>0.05). CONCLUSIONS: D allele positively affected the serum ACE level but there was no association between IL-1B genotype and its levels. ACE gene polymorphism has an important role in determining the response to EPO and progression of CKD. Pre-treatment screening for genotype may help in predicting the patients at risk and poor responders.

Gitelman Syndrome: Presenting During Pregnancy with Adverse Foetal Outcome.

Gitelman syndrome (GS) is a rare autosomal recessive salt-losing tubulopathy. The incidence of Gitelman syndrome is 25 cases in 1 million among western population. This patient presented with loose stool, vomiting and sudden onset quadriparesis. Investigations revealed hypokalaemia, metabolic acidosis, hypomagnesaemia, hypocalciuria, hypermagnesuria. Symptoms and hypokalemia improved after starting oral magnesium and potassium supplements. But the patient again presented with symptomatic hypokalemia and delivered a still born foetus with hydrocephalus. Patient was put on potassium sparing diuretics along with supplements and thereafter, has been asymptomatic. There have been very few case reports on Gitelman syndrome in pregnancy and most of them show favourable outcomes. This is a rare case report of a pregnant female with Gitelman syndrome with foetal loss.

Kallman Syndrome.

Kallman syndrome (KS) is a rare genetic disorder characterized clinically by failure to attain puberty or failure to fully complete it along with an absent or impaired sense of smell with absence of bilateral olfactory bulbi and sulci alongwith absent olfactory tracts. Only very few cases of Kallman syndrome have been reported in females in Indian population.

Families of Pseudohypoparathyroidism presenting as Seizure.

Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by variable insensitivity to parathyroid hormone. We describe two cases of 22 year male and 24 year female who have typical clinical features of Albright's hereditary osteodystrophy (AHO). Laboratory investigation revealed evidence of pseudohypoparathyroidism and skeletal survey showed shortening of the metacarpals and metatarsals.

Azetidin-2-ones, synthon for biologically important compounds.

Azetidin-2-one, a four-membered cyclic lactam (beta-lactam) skeleton has been recognised as a useful building block for the synthesis of a large number of organic molecules by exploiting the strain energy associated with it, in addition to its use in the synthesis of a variety of beta-lactam antibiotics. Efforts have been made in exploring such new aspects of beta-lactam chemistry using enantiomerically pure beta-lactams as versatile intermediates for the synthesis of aromatic beta-amino acids and their derivatives, peptides, polyamines, polyamino alcohols, amino sugars and polyamino ethers. The development of methodologies based on beta-lactam nucleus is now referred as 'the beta-lactam synthon methods'. The selective bond cleavage of the strained ring coupled with further interesting transformation render this fascinating molecule as a powerful building block. This provides an access to diverse structural type of synthetic target molecules lacking beta-lactam ring structure. This review provides an account of synthesis of organic compounds having biological significance at the same time lacking beta-lactam ring, by using beta-lactam as synthon.

Effect of soybean flour on exocrine function in rat pancreas transplant with bladder drainage.

The urinary output of trypsin, chymotrypsin, elastase, and amylase by rats with a pancreas transplant and bladder drainage was determined after injection with cholecystokinin (CCK) or by feeding diets containing high (raw soy flour) or low (heated soy flour) trypsin inhibitor activity. The injection of CCK produced a significant increase in the urinary output of all four enzymes. Rats were fed heated or raw soy flour in three consecutive 10-day periods in the following sequence: period 1, heated soy flour; period 2, raw soy flour; period 3, heated soy flour. Replacing heated soy flour in period 1 with raw soy flour in period 2 caused a significant increase in the output of the four enzymes. Subsequent feeding with heated soy flour in period 3 resulted in a reduction in the output of trypsin, chymotrypsin, and elastase to levels that were not significantly different from that observed in period 1. Although amylase output was also reduced in period 3, it did not return to the level noted in period 1. These results are consistent with the roles that CCK and trypsin inhibitors are believed to play in the negative feedback control of pancreatic exocrine function. A similar approach might be employed with humans who have undergone a pancreas transplant with bladder drainage.

Quantification of cerebellar structures with MRI.

Methodological issues have limited neuroimaging studies of cerebellar structures. In this article we describe a method that addresses some of these limitations and phantom studies that examine the validity of the image manipulations. We compared volumes derived from 3D Spoiled Gradient Recalled Acquisition MR images sliced with respect to three different alignment methods: one based on cerebellar landmarks, another on cerebral landmarks and a third on the plane of acquisition. Examination of coefficients of variation, coefficients of error and convergent validity suggests that although regional cerebellar volumes based on cerebellar landmarks provide the best estimates of the true volumes, observed differences between volume measurements from alignments based on cerebellar or cerebral landmarks were generally not significant and were inconsequential. In this case, the measure was improved with alignment along local, relevant cerebellar landmarks. A set of phantom experiments showed that realignment, reslicing and interpolation in 3-dimensional image processing exerted, at most, trivial distortion on the estimates of actual object volumes.

A comparative clinico-pathological study of single dose ROM in paucibacillary leprosy patients with 1-3 skin lesions.

A controlled clinical and histopathological study was carried out to compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin 400 mg plus minocycline 100 mg (ROM) administered as a single dose with that of standard WHO/MDT-PB six months' regimen with regard to resolution of lesion clinically and histopathologically. Skin biopsy was performed at the intake and at 6 months. The study subjects were 32 previously untreated, smear-negative patients, without nerve trunk involvement and having 1-3 skin lesions. The results were analyzed for mean clinical score for marked, moderate and no improvement and mean histopathological score was graded as active, resolving and complete resolution, according to granuloma fraction at the end of 6 months. Marked clinical improvement was seen in 25% and 12%, moderate improvement in 50% and 56% patients treated with ROM and standard regimens respectively. Histopathologically, activity was seen in 62.5% and 43.7% and resolution of granuloma in 25% and 31.2% in the ROM and standard regimens respectively. Both the regimens were equally efficacious in the reduction of clinical score and granuloma fraction. No adverse drug reactions or reversal reactions were seen during the study period in both the groups.