Intractable Diarrhea from Carbamazepine

Diarrhea has been reported as an early, mild, and uncommon complication of carbamazepine (CBZ) therapy. We report three cases of intractable diarrhea induced by CBZ necessitating discontinuation of the drug.     

Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer.

PURPOSE: Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors including colorectal cancer. However, there is no study examining the relationship of legumain expression to clinocopathologic and biological variables in colorectal cancers. EXPERIMENTAL DESIGN: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry. We also did Western blotting analysis on three additional colorectal cancers and three colonic cell lines. RESULTS: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05). Legumain expression was positively related to poorer differentiation/mucinous carcinoma (P = 0.04), higher degree of necrosis (P = 0.03) and apoptosis (P < 0.0001), positive proliferating cell nuclear antigen (P < 0.0001) and p53 expression (P = 0.049), and had a positive tendency towards stromelysin 3 (P = 0.058) and PINCH positivity (P = 0.05). The patients with tumors that showed both weak and lower percentage of the legumain expression, either in tumor (P = 0.01) or in stroma (P = 0.04), had a better prognosis. CONCLUSIONS: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients.     

Post-ischemic treatment with a lazaroid (U74389G) prevents transient global ischemic damage in rat hippocampus

Abstract

The ability of an experimental lazaroid, U74389G, to prevent damage to hippocampal CA 1 cytoarchitecture due to transient global ischemia was studied by light and electron microscopy. Post-ischemic rats were given a single i.p. dose of lazaroid (6 or 18 mg kg-¹) at 5 min after revival by cardiopulmonary resuscitation (CPR). Without lazaroid treatment the number of normal-appearing neurons in the CA1 region declined from a normal value of 75.49± 2.21 to 8.40± 10.08 per 100 μ,m² on day 7 after the ischemic episode, and there was extensive damage visible in the cytoarchitecture of this region. In lazaroid treated rats, the normal cytoarchitecture was retained and the number of normal-appearing cells was maintained at 15.1O± 2.22 per 100 ¼,m²? Ultrastructure studies indicated that pyknotic pyramidal cells laden with Pysosomal aggregates were common in untreated post-ischemic rats but rare in lazaroid-treated rats. These results indicate that U74389G maintained the structural integrity of this region of the brain after transient global ischemia and suggest that this lazaroid may be an effective neuroprotectant. [Neural Res 1997; 19: 431-434]     

New 6-bromoimidazo[1,2-a]pyridine-2-carbohydrazide derivatives: synthesis and anticonvulsant studies

In the present work, we report the facile synthesis and anticonvulsant study of new imidazo[1,2-a]pyridines carrying biologically active hydrazone functionality (3a–3e) and suitably substituted 1,2,4-triazole moieties (4, 5a–5d, 6, and 7a–7d). The newly synthesized intermediates and final compounds were characterized by various spectral techniques such as FTIR, ¹H NMR, ¹³C NMR, and mass spectral and elemental analysis studies. The in vivo anticonvulsant study of the target compounds were carried out following maximal electroshock seizure and subcutaneous pentylene tetrazole methods, while their toxicity study was performed following rotarod method by taking 20, 40, and 100 mg/kg dose levels. Most of the new compounds displayed remarkable anticonvulsant properties at these doses. Particularly, compounds 3b and 4 carrying hydrogen bond donor groups, viz. hydroxyl and amine moieties respectively, exhibited complete protection against seizure and their results are comparable to that of standard drug diazepam. Further, the motor impairment study revealed that all the compounds are nontoxic upto 100 mg/kg.     

Three dimensional coupled reaction–diffusion modeling of calcium and inositol 1,4,5-trisphosphate dynamics in cardiomyocytes

Nanoparticles have shown great promise in improving cancer treatment efficacy by changing the intracellular calcium level through activation of intracellular mechanisms. One of the mechanisms of the killing of the cancerous cell by a nanoparticle is through elevation of the intracellular calcium level. Evidence accumulated over the past decade indicates a pivotal role for the IP₃ receptor mediated Ca²⁺ release in the regulation of the cytosolic and the nuclear Ca²⁺ signals. There have been various studies done suggesting the role of IP₃ receptors (IP₃R) and IP₃ production and degradation in cardiomyocytes. In the present work, we have proposed a three-dimensional unsteady-state mathematical model to describe the mechanism of cardiomyocytes which focuses on evaluation of various parameters that affect these coupled dynamics and elevate the cytosolic calcium concentration which can be helpful to search for novel therapies to cure these malignancies by targeting the complex calcium signaling process in cardiomyocytes. Our study suggests that there are other factors involved in this signaling which can increase the calcium level, which can help in finding treatment for cancer. The cytosolic calcium level may be controlled by IP₃ signaling, leak, source influx of calcium (σ) and maximum production of IP₃ (V_P). We believe that the proposed model suggests new insight into finding treatment for cancer in cardiomyocytes through elevation of the cytosolic Ca²⁺ concentration by various parameters like leak, σ, V_P and especially by other complex cell signaling dynamics, namely IP₃ dynamics.

We propose a three-dimensional unsteady-state mathematical model to describe the mechanism of cardiomyocytes.     

Evaluation of spinal evoked potentials: a model for assessment of spinal cord function in isolation

Spinal evoked potentials were recorded from the dorsal columns of in vitro mouse hemicord preparations. The response of these potentials to different periods of hypoxia was studied. A decrease in amplitude of the potential to 50% and 10% of pre-hypoxia reference occurred after 3.19 ± 1.36 and 7.3 ± 2.97 min, respectively. Complete recovery of the potential was seen in specimens exposed to 5 and 10 min of hypoxia. Incomplete recovery occurred with exposure to longer periods of hypoxia. In preparations that remained isoelectric for less than 5 min total recovery was seen.     

Immunomodulatory Activity of Achyranthes aspera on the Elicitation of Antigen-Specific Murine Antibody Response

The extract of Achyranthes aspera Linn. (Amaranthaceae) was found to enhance the induction of ovalbumin (OVA)- specific humoral antibody response in mice, on intraperitoneal injection of extract along with OVA. The antibody response was evaluated by passive cutaneous anaphylaxis (PCA) and ELISA for IgE and other classes or subclasses of antibodies, respectively. Furthermore, the plant extract was found to increase the induction of OVA-specific antibody response in a dose-dependent manner. A significant elevation of IgM, IgG 1 and IgG 3 antibodies was observed (p &lt; 0.01); however, interestingly, the anti-OVA PCA titers were suppressed. The adjuvant property of the extract was further examined in different strains of mice and a significant elevation of the OVA-specific IgG antibody response in all strains tested was found. When the extracts of different parts of the herb were tested, the seed and root extracts appeared to exhibit relatively higher activity. These results confirm the immunostimulatory properties of Achyranthes aspera.     

Technology as a 'major driver' of health care costs: a cointegration analysis of the Newhouse conjecture

Per capita real income on the demand-side and technological change, proxied by total R&D and health R&D spending, on the supply-side are hypothesized as major drivers of per capita real health care expenditure in the US during the 1960-1997 period. The findings are robust to a battery of unit root and cointegration tests. They support the Newhouse [Journal of Economic Perspectives 6 (1992) 3] conjecture that technological change is a major escalator of health care expenditure and confirm a significant and stable long-run relationship among per capita real health care expenditure, per capita real income and broad-based R&D expenditures. Policy implications are noted.