Senile systemic amyloidosis--a case report

An 85 years old female presented with acute pain and weakness in left lower extremity and doppler evidence of femoropopliteal block was made which subsequently proved fatal. Necropsy revealed extensive amyloid deposition in the heart and amyloid angiopathy in rest of the organs.     

IgM nephropathy in adults: incidence and correlation with electron microscopic features

IgM nephropathy is characterised on light microscopy (LM) by variable features of normal glomeruli to mesangial hypercellularity; and immunofluorescence (IF) deposits of LgM. Our aim was to study the incidence of IgM nephropathy in adults with primary glomerular disease, with correlation to electron microscopy (EM) features. All adults presenting with proteinuria glomerular hematuria underwent renal biopsy. We excluded patients with systemic diseases and post-infectious glomerulonephritis. All the specimens were evaluated by LM, IF and EM. Our series had 146 cases. Of the 42 cases diagnosed on LM as minimal change disease, mesangial deposition of IgM was present in 11 cases. In addition there were seven cases of mesangioproliferative glomerulonephritis with mesangial IgM deposition. Thus, there were a total of 18 cases of IgM nephropathy (12.3%). Only six of these 18 cases showed typical electron dense deposits in the mesangium on EM. We feel that IgM nephropathy is probably a separate pathological entity, comprising 12.3% of all adults with primary chronic glomerulopathy. Electron dense deposits are seen in only about a third of these cases.     

Enantioselective N-Demethylation and Hydroxylation of Sibutramine in Human Liver Microsomes and Recombinant Cytochrome P-450 Isoforms

The enantioselective metabolism of sibutramine was examined using human liver microsomes (HLM) and recombinant cytochrome P-450 (CYP) isoforms. This drug is metabolized to N-mono-desmethyl- (M1) and N,N-di-desmethylsibutramine (M2), and subsequent hydroxylation results in hydroxyl M1 (HM1) and hydroxyl M2 (HM2). No significant difference was noted in formation of M1from sibutramine between R- and S-sibutramine in HLM. However, S-enantiomers of M1 and M2 were preferentially metabolized to M2, HM1, and HM2compared to R-enantiomers in HLM, and intrinsic clearance (Cl_int) ratios of S-enantiomers/R-enantiomers were 1.97, 4.83, and 9.94 for M2, HM1, and HM2, respectively. CYP3A4 and CYP3A5 were only involved in the formation of M1, whereas CYP2B6 and CYP2C19 were responsible for all metabolic reactions of sibutramine. CYP2C19 and CYP3A5 displayed catalytic preference for S-sibutramine to S-M1, whereas CYP2B6 and CYP3A4 showed little or no stereoselectivity in metabolism of sibutramine to M1. In the case of M2 formation, CYP2B6 metabolized S-M1 more rapidly than R-M1 with a Cl_int ratio of 2.14. However, CYP2C19 catalyzed less S-M1 than R-M1 and the Cl_int ratio of S-M1 to R-M1 was 0.65. The most significant enantioselectivity was observed in formation of HM1 from M1, and HM2 from M2. CYP2B6 and CYP2C19 exhibited preferential catalysis of formation of hydroxyl metabolites from S-enantiomers rather than R-enantiomers. These results indicate that S-sibutramine was more rapidly metabolized by CYP isoforms than R-sibutramine, and that enantioselective metabolism needs to be considered in drug interactions involving sibutramine and co-administered drugs.     

Volvulus of ileal S-pouch: A rare complication of ileal pouch anal anastomoses

INTRODUCTION

Ileal pouch anal anastomosis (IPAA) after total proctocolectomy is a frequently performed surgery for medically refractory ulcerative colitis (UC). Volvulus of the ileal pouch as a complication of IPAA is extremely rare. We present a case of volvulus of S-type ileal pouch.

PRESENTATION OF CASE

A 28 year old male, with history of total proctocolectomy with IPAA for severe UC in 2009 presented with signs of bowel obstruction. Emergency laparotomy was done and a volvulus of the S-type ileal pouch was derotated and pouchpexy done.

DISCUSSION

The IPAA has a wide spectrum of complications, with obstruction of proximal small bowel occurring frequently. Volvulus of the ileal pouch is extremely rare with only 3 reported cases. Early diagnosis and intervention is important to salvage the pouch. Computed tomography (CT) may aid the diagnosis in stable patients.

CONCLUSION

The diagnosis of ileal pouch volvulus although rare, should be kept in mind when dealing with patients complaining of recurrent obstruction following IPAA.     

Duplex PCR Assay for Identification of Tissue of Cattle and Buffalo Origin Targeting Mitochondrial Cytochrome b Gene

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The aim of this study was to develop PCR assay for simultaneous detection of tissues from cattle and buffalo...     

Hormone therapy and antioxidant vitamins do not improve endothelial vasodilator function in postmenopausal women with established coronary artery disease: a substudy of the Women's Angiographic Vitamin and Estrogen (WAVE) trial

We measured flow-mediated dilation (FMD) by high-resolution brachial ultrasound in 61 women who participated in the Women's Angiographic Vitamin and Estrogen (WAVE) trial, a randomized controlled trial. There were no significant differences in the baseline demographics of women receiving hormone therapy (0.625 mg/day of conjugated equine estrogen plus 2.5mg of medroxyprogesterone acetate for women who had not had a hysterectomy) or placebo; or vitamins (400 IU of Vitamin E and 500 mg of Vitamin C twice daily) or placebo. Baseline FMD was impaired in all subjects (3.3+/-7.6%). Neither hormone therapy (4.1+/-5.2% at baseline, 4.2+/-5.0% at 3 months, and 4.1+/-6.5% at 34 months) nor antioxidant vitamins (3.0+/-8.3% at baseline; 3.5+/-4.6% at 3 months; 3.1+/-7.6% at 34 months) improved FMD (all p-values=NS). Endothelium-independent vasodilation, induced by nitroglycerin (NTG) was similar at baseline and was not affected by either therapy. In univariate and multivariate analysis, neither hormone therapy nor antioxidant vitamins were associated with FMD. Women with established coronary artery disease have impaired flow-mediated vasodilation of the brachial artery that does not improve after 3 months or up to 34 months of treatment with postmenopausal hormone therapy or antioxidant vitamins.     

Dual depolarization responses generated within the same lateral septal neurons by TRPC4-containing channels

In the central nervous system, canonical transient receptor potential (TRPC) channels have been implicated in mediating neuronal excitation induced by stimulating metabotropic receptors, including group 1 metabotropic glutamate receptors (mGluRs). Lateral septal (LS) neurons express high levels of TRPC4 and group I mGluRs. However, to what extent native TRPC4-containing channels (TRPC4-cc) are activated as well as the impact of different levels of TRPC4-cc activation on neuronal excitability remain elusive. Here, we report that stimulating LS neurons with group I mGluR agonist, (S)-3,5-DHPG, causes either an immediate increase in firing rate or an initial burst followed by a pause of firing, which can be correlated with below-threshold-depolarization (BTD) or above-threshold-plateau-depolarization (ATPD), respectively, in whole-cell recordings. The early phase of BTD and the entire ATPD are completely absent in neurons from TRPC4^?/? mice. Moreover, in the same LS neurons, BTD can be converted to ATPD at more depolarized potentials or with a brief current injection, suggesting that BTD and ATPD may represent partial and full activations of TRPC4-cc, respectively. We show that coincident mGluR stimulation and depolarization is required to evoke strong TRPC4-cc current, and Na⁺ and Ca²⁺ influx, together with dynamic changes of intracellular Ca²⁺, are essential for ATPD induction. Our results suggest that TRPC4-cc integrates metabotropic receptor stimulation with intracellular Ca²⁺ signals to generate two interconvertible depolarization responses to affect excitability of LS neurons in distinct fashions.