Liposomal formulation of curcumin attenuates seizures in different experimental models of epilepsy in mice

Contemporary research indicates promising anticonvulsant effect of curcumin. However, its poor oral bioavailability is a major hindrance toward its pharmacological action. Thus, this study was carried out to evaluate the acute effect of liposome‐entrapped curcumin on increasing current electroshock seizures (ICES) test, pentylenetetrazole (PTZ)‐induced seizures, and status epilepticus in mice. Liposome‐entrapped curcumin in doses 25 and 50 mg/kg demonstrated significant increase in seizure threshold current and latency to myoclonic and generalized seizures in ICES test and PTZ‐induced seizures, respectively. Similarly, liposomal‐entrapped curcumin also increased the latency to the onset and decreased the duration of seizures during status epilepticus in mice. To conclude, liposomal‐entrapped curcumin possesses anticonvulsant activity against status epilepticus in mice.     

Metastatic Differentiated Thyroid Carcinoma: ClinicopathologicalProfile and Outcome in an Iodine Deficient Area

Reports on metastatic differentiated carcinoma in endemic goiter regions are scarce. The aim of this study was to look into the clinicopathological profile and outcome of patients with metastatic differentiated thyroid carcinoma (DTC) of endemic origin. This was a retrospective study of 28 cases of metastatic DTC out of a total of 140 DTC patients managed between 1990 and June 1999. Demographic data, clinicopathological profile, operative and radioiodine ablation therapy details, and follow-up findings were noted. The overall incidence of distant metastases in our series was 20%. Mean age was 48.5 +/- 12.8 years (32.1%patients were < 45 years). Most metastases were detected synchronously (85.7%) and were multiple, with the skeletal system being the commonly affected site. Out of 22 cases having skeletal metastases, 6 patients were young (< 45 years). Though most patients with skeletal metastases had follicular carcinoma (FTC), 4 cases had papillary thyroid cancer (PTC). Near total or total thyroidectomy was done in 26 cases. Sixteen patients required regional lymph node dissection. Resection of metastases was performed in 9 cases.Histopathological diagnosis was PTC, FTC, and poorly differentiated carcinoma in 32.1%, 50.0%, and 17.9% of cases, respectively. Most patients had good symptomatic palliation following administration of I131 therapy. In 17.9% of cases there were locoregional recurrences. There was an overall 28.6% mortality. Two patients expired in the perioperative period. Six others died in follow-up (all within 3-9 months). In contrast to iodine sufficient regions, the incidence of metastases was high; the majority of cases had synchronous, symptomatic skeletal metastases. Skeletal metastases were not infrequent even in cases of PTC and in young patients. One-third of the cases were young. Though survival was poor despite aggressive management, significant symptomatic palliation could be achieved in most cases.     

Determination of hand and palm area as a ratio of body surface area in Indian population

Background:

Accurate estimation of body surface area (BSA) burn is important. In small and patchy burns, the patient''s hand is used to estimate percentage of burn which is traditionally considered as 1%. There is discrepancy about what percentage of TBSA is constituted by the palm and hand. Therefore, this study was designed to determine correctly the TBSA represented by the palmar surface of the entire hand and palm in the Indian population.

Material and Methods:

300 healthy adult (male and female) and 300 healthy children (male and female) were included in the study. TBSA was calculated using DuBois formula and hand and palm surface area was calculated using hand tracing on plain paper. The hand/palm percentage of BSA (ratio) was determined by dividing hand/palm surface area by total BSA.

Results:

The mean hand and palm ratio for adults was 0.92% and 0.50%, respectively. The mean hand and palm ratio in children was 1.06% and 0.632%, respectively.

Conclusion:

The hand area (palm plus digits) is more closely represented to 1% of TBSA in Indian population.     

Calpeptin provides functional neuroprotection to rat retinal ganglion cells following Ca2+ influx

Apoptosis of retinal ganglion cells (RGCs) impairs vision in glaucoma patients. RGCs are also degenerated in multiple sclerosis (MS), resulting in loss of visual perception in MS patients. We examined the involvement of calpain and caspase cascades in apoptosis of the rat retinal ganglion cell line RGC-5 following 24 h of exposure to 250 nM ionomycin (IMN) or 300 units/ml interferon-gamma (IFN-gamma) and then evaluated functional neuroprotection with 2 microM calpeptin (CP, a calpain-specific inhibitor). Morphological and biochemical features of apoptosis were detected in RGC-5 cells following exposure to IMN or IFN-gamma. Fura-2 assay determined significant increases in intracellular free [Ca2+] following exposure to IMN or IFN-gamma. Pretreatment with CP for 1 h prevented Ca2+ influx, proteolytic activities, and apoptosis in RGC-5 cells. Western blot analyses showed an increase in activities of calpain and caspase-12, upregulation of Bax:Bcl-2 ratio, release of cytochrome c from mitochondria, and increase in caspase-9 and caspase-3 activities during apoptosis. Increased caspase-3 activity was also confirmed by a colorimetric assay. Activation of caspase-8 and cleavage of Bid to tBid in RGC-5 cells following exposure to IFN-gamma indicated co-operation between extrinsic and intrinsic pathways of apoptosis. Patch-clamp recordings showed that pretreatment with CP attenuated apoptosis and maintained normal whole-cell membrane potential, indicating functional neuroprotection. Taken together, our results demonstrated that Ca2+ overload could be responsible for activation of calpain and caspase cascades leading to apoptotic death of RGC-5 cells and CP provided functional neuroprotection.     

Interdialytic hypertension-an update

The reference standard for diagnosing hypertension among hemodialysis patients is 44-hour interdialytic ambulatory blood pressure (BP) recording. However, a more practical way to diagnose and manage hypertension is to measure home BP over the interdialytic interval. In contrast to pre- and postdialysis BP recordings, measurements of BP performed outside the dialysis unit correlate with the presence of left ventricular hypertrophy and directly and strongly with all-cause mortality. Hypervolemia that is not clinically obvious is the most common treatable cause of hypertension among patients with end-stage renal disease; thus, volume control should be the initial therapy to treat hypertension in most hemodialysis patients. To diagnose hypervolemia, continuous blood volume monitoring is emerging as an effective and simple technique. Reducing dietary and dialysate sodium is an often overlooked strategy to improve BP control. Although definitive randomized trials that show cardiovascular benefits of BP lowering among hypertensive hemodialysis have not been performed, emerging evidence suggests that lowering BP might reduce cardiovascular events. The treatment should be guided by BP obtained outside the dialysis unit because predialysis and postdialysis BP are quite variable and agree poorly with measurements obtained outside the dialysis unit. Although the appropriate level to which BP should be lowered remains elusive, current data suggest that interdialytic ambulatory systolic BP should be lowered to <130 mm Hg and averaged home systolic BP to <140 mm Hg. Antihypertensive drugs will be required by most patients receiving thrice weekly dialysis for 4 hours. Beta blockers, dihydropyridine calcium blockers, and agents that block the renin-angiotensin system appear to be effective in lowering BP in these patients.     

Pulmonary valve preservation in Tetralogy of Fallot with a mildly hypoplastic annulus-should we do it?

Background  

The decision to preserve the pulmonary valve during intracardiac repair of Tetralogy of Fallot [TOF] is traditionally based on the intra-operative measurement of pulmonary annulus by a Hegar dilator as per Rowlatt’s table. We sought to evaluate if there can be flexibility in not using a transannular patch repair in Indian population with mildly hypoplastic pulmonary annulus.     

A comprehensive work up for an asthenozoospermic man with repeated intracytoplasmic sperm injection (ICSI) failure

Infertility affects about 15-20% couples attempting pregnancy and in about half cases the problem lies in the male. Among the sperm parameters, linear progressive motility is one of the most important predictors of fertility potential. Though genetic and chromosomal abnormalities are important aetiological factors in the pathogenesis of male infertility, the mechanism involved in impaired sperm motility is poorly understood. Here we report mitochondrial DNA (mtDNA) mutations with increased seminal reactive oxygen species (ROS) levels and higher DNA fragmentation level in the sperm resulting in decreased ATP production which plays an important role in sperm motility defect. Thus it is important to understand the aetiology of asthenozoospermia and to distinguish if infertile men harbour nuclear or mtDNA mutation as they are very important prognostic markers. This case study also highlights that routine semen parameters are very modest predictors of fertility outcome but ROS estimation and DNA integrity analysis by Comet assay have better diagnostic and prognostic capabilities. Thus this study is a detailed and comprehensive workup of an infertile asthenozoospermic male.     

Identification and initial characterization of 5000 expressed sequenced tags (ESTs) each from adult human normal and osteoarthritic cartilage cDNA libraries

OBJECTIVE: To prepare, sequence and analyse adult human cartilage cDNA libraries to study the gene expression pattern between normal and osteoarthritic cartilage. METHODS: Poly A(+)RNA from adult human normal and osteoarthritic articular cartilage was isolated and used to prepare cDNA libraries. Approximately 5000 ESTs from each library were sequenced and analysed using bioinformatic tools. The expression of select genes was confirmed by Northern blot and in situ hybridization analysis. RESULTS: Multiple gene families including several classical cartilage matrix protein encoding genes were identified. Approximately 28-40% of the genes sequenced from these libraries were novel, while half of the genes encoded known proteins and 4-6% of the genes encoded novel homologs of known proteins. Several known genes, whose expression has not been reported previously in cartilage, were also identified. We have confirmed the cartilage expression of three known (CTGF, CTGF-L and clusterin) and two novel homologs of known genes (PCPE-2 and Gal-Nac transferase) by Northern blot and in situ hybridization analysis. CONCLUSION: This is the first report of the preparation and sequencing of cDNA libraries from adult human normal and osteoarthritic articular cartilage. Further analysis of genes identified from these libraries may provide molecular targets for diagnosis and/or treatment of osteoarthritis (OA).