Zinc-naproxen complex: synthesis,physicochemical and biological evaluation

Naproxen has a propensity to cause ulcers whereas zinc ions are known to possess an anti-ulcer and anti-inflammatory activity. Therefore, zinc complex of naproxen was prepared by adding zinc sulfate to an aqueous solution of sodium naproxen and its structure was characterized by IR, ¹H NMR and ¹³C NMR, UV, DSC, atomic absorption spectroscopy, and elemental analysis. Anti-inflammatory studies, using the carrageenan-induced hind paw oedema showed that there was a significant difference (P<0.05, ANOVA plotted by Dunnet’s test) in the anti-inflammatory activity of naproxen, its zinc complex, and the physical mixture of naproxen and zinc sulfate. In addition, zinc complex of naproxen showed a significant reduction in ulcers (lesion index (LI)) as compared to that of naproxen and physical mixture of naproxen and zinc sulfate. Thus, the use of the complex may be preferable to naproxen alone.     

Combined procedures in laparoscopic surgery

With advancements in minimal access surgery, combined laparoscopic procedures are now being performed for treating coexisting abdominal pathologies at the same surgery. In our center, we performed 145 combined surgical procedures from January 1999 to December 2002. Of the 145 procedures, 130 were combined laparoscopic/endoscopic procedures and 15 were open procedures combined with endoscopic procedures. The combination included laparoscopic cholecystectomy, various hernia repairs, and gynecological procedures like hysterectomy, salpingectomy, ovarian cystectomy, tubal ligation, urological procedures, fundoplication, splenectomy, hemicolectomy, and cystogastrostomy. In the same period, 40 patients who had undergone laparoscopic cholecystectomy and 40 patients who had undergone ventral hernia repair were randomly selected for comparison of intraoperative outcomes with a combined procedure group. All the combined surgical procedures were performed successfully. The most common procedure was laparoscopic cholecystectomy with another endoscopic procedure in 129 patients. The mean operative time was 100 minutes (range 30-280 minutes). The longest time was taken for the patient who had undergone laparoscopic splenectomy with renal transplant (280 minutes). The mean hospital stay was 3.2 days (range 1-21 days). The pain experienced in the postoperative period measured on the visual analogue scale ranged from 2 to 5 with a mean of 3.1. Of 145 patients who underwent combined surgical procedures, 5 patients developed fever in the immediate postoperative period, 7 patients had port site hematoma, 5 patients developed wound sepsis, and 10 patients had urinary retention. As long as the basic surgical principles and indications for combined procedures are adhered to, more patients with concomitant pathologies can enjoy the benefit of minimal access surgery. Minimal access surgery is feasible and appears to have several advantages in simultaneous management of two different coexisting pathologies without significant addition in postoperative morbidity and hospital stay.     

Fetal hippocampal CA3 cell grafts enriched with fibroblast growth factor-2 exhibit enhanced neuronal integration into the lesioned aging rat hippocampus in a kainate model of temporal lobe epilepsy

Aging impairs the conduciveness of the lesioned hippocampus for robust survival of neurons derived from homotopic fetal cell grafts (Zaman and Shetty, Neuroscience 109:537-553, 2002), suggesting a need for graft augmentation in fetal graft-mediated therapeutic strategies for the lesioned aging hippocampus. We hypothesize that pretreatment and grafting of donor hippocampal CA3 cells with fibroblast growth factor-2 (FGF-2) considerably enhances graft neuronal integration into the lesioned CA3 region of the aging hippocampus. We employed the optical fractionator cell counting method and quantified the number of surviving cells and neurons derived from 5'-bromodoxyuridine-labeled embryonic day 19 CA3 cell grafts pre-treated and transplanted with FGF-2 into the lesioned CA3 region of the middle-aged and aged rat hippocampus at 4 days post-lesion. In both middle-aged and aged hippocampus, pre-treatment and transplantation of CA3 cell grafts with FGF-2 resulted in a robust yield of surviving cells (72-80% of injected cells) and neurons (62-69% of injected cells) from grafts. The overall yield was dramatically greater than the yield observed earlier from standard (untreated) fetal CA3 cell grafts into the lesioned aging hippocampus but was highly comparable to that observed for standard fetal CA3 cell grafts into the lesioned young hippocampus (Zaman and Shetty, Neuroscience 109:537-553, 2002). Thus, a robust neuronal integration from fetal CA3 cell grafts can be achieved into the lesioned CA3 region of the aging hippocampus with a simple pre-treatment and grafting of donor fetal CA3 cells with FGF-2. These results have implications toward the development of suitable cell grafting strategies for repair of the lesioned aging hippocampus in neurodegenerative diseases, particularly the temporal lobe epilepsy, stroke, and Alzheimer's disease.     

Impaired sequence learning in carriers of the DYT1 dystonia mutation

Previous positron emission tomography (PET) studies have shown that nonmanifesting carriers of the DYT1 dystonia mutation express an abnormal pattern of resting glucose metabolism. To determine whether motor behavior is impaired in these subjects, we compared movement and sequence learning in 12 clinically unaffected DYT1 carriers with 12 age-matched controls. Regional differences in brain function during task performance were assessed with simultaneous H(2) (15)O/PET. We found that motor performance was similar in the DYT1 and control groups, with no significant differences in movement time and spatial accuracy measured during each of the tasks. In contrast, sequence learning was reduced in gene carriers relative to controls (p < 0.01). PET imaging during motor execution showed increased activation in gene carriers (p < 0.001, uncorrected) in the left premotor cortex and right supplementary motor area, with concomitant reduction in the posterior medial cerebellum. During sequence learning, activation responses in DYT1 carriers were increased in the left ventral prefrontal cortex, and lateral cerebellum. These findings suggest that abnormalities in motor behavior and brain function exist in clinically nonmanifesting DYT1 carriers. Although localized increases in neural activity may enable normal movement execution in these subjects, this mechanism may not compensate for their defect in sequence learning.     

Thrombotic occlusion of Bjork-Shiley prosthetic aortic valve

Thrombotic occlusion of a prosthetic Bjork-Shiley valve is a potentially fatal complication. We present the case of a male, 62 years of age, diagnosed with thrombotic occlusion of prosthetic Bjork-Shiley aortic valve approximately 17 years post implantation. A brief review of the literature focusing on potential risk factors associated with the development of this condition and currently available diagnostic modalities used for evaluation and treatment are presented.     

Effect of vaginally administered fumagillin on the morphology of implantation stage endometrium in the rhesus monkey

Intravaginal administration of an anti-angiogenic agent, fumagillin, during blastocyst implantation, inhibits pregnancy establishment in a dose-related manner in the rhesus monkey. In the present study, mated female rhesus monkeys were vaginally inserted with tampons containing vehicle (group 1; n = 5) and test agent (fumagillin, 4 mg/animal; group 2; n = 6) on cycle day 20, and endometrial tissue samples were collected on cycle day 24 from all monkeys and processed for morphometric and ultrastructural analysis. Concentrations of estradiol-17beta, progesterone and chorionic gonadotrophin in peripheral circulation were determined. From serum profiles of hormones, two monkeys in group 1, and one animal in group 2 appeared pregnant. Endometrial morphology revealed histologic evidence of pregnancy in three of six fumagillin-treated animals, while other three fumagillin-treated animals showed degenerative changes in glands and venules along with marked extravasation. It is possible that the function of corpus luteum was affected by fumagillin treatment resulting in inadequate progesterone production (p <0.05), and consequent inadequate endometrial secretory preparation and receptivity, as revealed from decline in apical movement of vacuoles (p <0.05) and increase (p <0.05) in extravasation of red cells and leukocytes.     

Asiaticoside-induced elevation of antioxidant levels in healing wounds

Asiaticoside derived from the plant Centella asiatica is known to possess good wound healing activity. Enhanced healing activity has been attributed to increased collagen formation and angiogenesis. Since antioxidants have been reported to play a significant role in the wound healing process we studied the effect of asiaticoside on the levels of certain antioxidants in the wound so as to explore the possible involvement of such a mechanism in the asiaticoside induced wound healing. Asiaticoside application (0.2%, topical) twice daily for 7 days to excision-type cutaneous wounds in rats led to increased enzymatic and non-enzymatic antioxidants, namely superoxide dismutase (35%), catalase (67%), glutathione peroxidase (49%), vitamin E (77%) and ascorbic acid (36%) in newly formed tissues. It also resulted in a several fold decrease in lipid peroxide levels (69%) as measured in terms of thiobarbituric acid reactive substance. However, continued application for 14 days showed no significant difference in these antioxidants compared with their values in vehicle treated wound tissue. It appears from the present study that asiaticosides enhanced induction of antioxidant levels at an initial stage of healing which may be an important contributory factor in the healing properties of this substance.