Morphine-induced macrophage apoptosis modulates migration of macrophages: use of in vitro model of urinary tract infection

BACKGROUND: Morphine has been reported to alter immune function. Morphine-induced macrophage apoptosis has been shown to contribute to altered immune status in an opiate milieu. We studied the effect of morphine-induced macrophage apoptosis on the migration of macrophages. Because urinary tract infection (UTI) is one of the commonest infections to evoke an inflammatory response; i.e., migration of neutrophils and monocytes to the site of infection, we used an in vitro model of UTI to test our hypothesis. MATERIALS AND METHODS: We carried out both in vivo and in vitro studies. Mice of the FVB/N strain were treated with morphine for short (three doses, 24 hours) and long (11 doses, 96 hours) durations, and their bone marrow cells were isolated. In addition, apoptotic macrophages were prepared by heat treatment. To simulate the in vitro model of UTI, E. coli-activated tubular cell (TC)-conditioned medium containing transforming growth factor-beta (TGF-beta) and macrophage-monocyte chemoattractant protein-1 (MCP-1) was used to test migration of macrophages across a filter in a modified Boyden chamber. In addition, migration of macrophages into the peritoneal cavity was evaluated in both control and morphine-treated states. The effect of morphine on apoptosis as well as migration was studied in murine macrophages and bone marrow cells. RESULTS: Morphine not only promoted apoptosis of bone marrow cells (20% apoptotic cells) but also inhibited their migration across the filter. Control cells showed minimal apoptosis but displayed greater migration. Similarly, heat-treated (apoptotic) cells showed minimal migration. In peritoneal macrophage studies, morphine treatment retarded migration. CONCLUSION: Morphine inhibits macrophage migration both in vivo and in vitro. This attenuated transmigration of macrophages seems to be secondary to the apoptotic effect of morphine.     

A case report of fatal dapsone-induced agranulocytosis in an Indian mid-borderline leprosy patient

Fatal agranulocytosis in an Indian male receiving 100mg of dapsone daily, hospitalized for mid-borderline leprosy in type I reaction with triple nerve paralysis is reported. Various case reports concerning dapsone-induced agranulocytosis are reviewed.     

Effects of tezosentan, a dual endothelin receptor antagonist, on the cardiovascular and renal systems of neonatal piglets during endotoxic shock

Background/Purpose: Endothelin is a potent mediator of the cardiovascular and renal systems. Studies have found that endothelin has an important role in regulating cardiac function and renal perfusion in neonates who are suffering from endotoxic shock. The authors believe that blockade of the endothelin response during endotoxemia will have a beneficial effect on neonatal cardiac and renal functions. In this study the authors have examined the effects of tezosentan, a dual endothelin-receptor antagonist, on the cardiovascular and renal systems of neonatal piglets during endotoxemia. Methods: Thirteen piglets were subjected to endotoxic shock and divided into a fluid-therapy group that received 0.9% normal saline and a group that received tezosentan (1 mg/kg/h). Mean arterial pressure (MAP), heart rate (HR), and glomerular filtration rate (GFR) were plotted at baseline, 1, 2, and 3 hours. Cardiac index (CI), renal blood flow (RBF), systemic vascular resistance (SVR), and renal vascular resistance (RVR) were obtained at baseline, 1, and 3 hours after baseline. Results: (P [lt ] .05 for 3 hours versus baseline and tezosentan versus fluid). Although fluid therapy in endotoxemia had no significant effect on MAP and RVR, it significantly increased HR (139 [plusmn] 17 to 246 [plusmn] 17 beats/min) and SVR (0.08 [plusmn] 0.05 to 0.33 [plusmn] 0.09 mm Hg/mL/min) and decreased CI (407 [plusmn] 208 to 98 [plusmn] 13 mL/min/kg), RBF (1.84 [plusmn] 0.38 to 0.97 [plusmn] 0.34 mL/min/kg kidney), and GFR (0.20 [plusmn] 0.05 to 0.11 [plusmn] 0.04 mL/min/kg) at 3 hours. The use of tezosentan also significantly increased HR (130 [plusmn] 14 to 220 [plusmn] 31 beats/min), but unlike in the fluid therapy group, there was a significant fall in MAP (77 [plusmn] 10 to 54 [plusmn] 9 mm Hg) and RVR (1.92 [plusmn] 0.44 to 1.77 [plusmn] 0.64 mm Hg/mL/min) and a less severe decrease in CI (482 [plusmn] 188 to 176 [plusmn] 67 mL/min/kg) at 3 hours. SVR, RBF, and GFR were maintained. Conclusions: Endotoxic shock affected cardiac and renal functions in both treatment groups. Fluid therapy alone could not prevent a statistically significant fall in CI, RBF, and GFR or prevent the increase in HR and SVR. Endothelin antagonism with tezosentan resulted in a statistically significant fall in MAP and RVR from baseline, not seen in the fluid-therapy group. CI and RBF were significantly higher, and MAP, SVR, and RVR were significantly lower when compared with the fluid-therapy group at 3 hours. GFR also was maintained at baseline with tezosentan. During endotoxemia, endothelin antagonism maintained renal and cardiac functions better than with fluid therapy alone.     

Angiotensin converting enzyme inhibition in chronic allograft nephropathy

BACKGROUND: Although angiotensin-converting enzyme inhibition has been shown to slow progression of chronic allograft nephropathy in animal models, no studies have examined its efficacy in humans. METHODS: We retrospectively analyzed 63 patients with biopsy-proven chronic allograft nephropathy who had > or =6 months dialysis-free follow-up at our institution. A total of 32 patients treated for > or =6 consecutive months with angiotensin-converting enzyme inhibition and/or angiotensin-receptor blocker (ARB) therapy (group 1) were compared with 31 patients not on these agents (group 2). RESULTS: Except for a higher incidence of hypertension (100 vs. 78%, P=0.005) in group 1, there were no significant differences in baseline clinical characteristics at time of biopsy. With a mean follow-up time of 27 months in both groups, 6 of 32 (19%) group 1 patients vs. 12 of 31 (39%) group 2 reached the primary endpoint of > or =50% increase in serum creatinine (P=0.10). Mean time to primary endpoint was 46.6 months in group 1 vs. 32.7 months in group 2 (P=0.07). Three of 32 (9%) of group 1 patients vs. 8 of 31 (26%) of group 2 returned to dialysis during this time (P=0.11). Significantly fewer patients in group 1 reached the combined secondary endpoint of allograft failure or death (9.4 vs. 35.5%, P=0.01); in addition, group 1 had a longer mean time to this endpoint (51.2 vs. 37.6 months, P=0.03). On multivariate analysis, the only predictor of progression to primary endpoint was a high baseline serum creatinine (P=0.02). No significant differences in hyperkalemia or anemia were found between the two groups. CONCLUSIONS: Angiotensin-converting enzyme inhibition/angiotensin-receptor blocker therapy is well tolerated in renal allograft recipients with chronic allograft nephropathy. It is associated with a trend of slowing renal insufficiency as well as a significant survival benefit in the combined endpoint of allograft failure or death.     

Idiopathic hypertrophic cranial pachymeningitis

Idiopathic hypertrophic cranial pachymeningitis is a rare form of fibrosing chronic inflammatory process of unknown etiology, which causes thickening of the intracranial dura mater. We present four patients with hypertrophic cranial pachymeningitis who presented with chronic headache and cranial nerve palsies. The diagnosis of idiopathic hypertrophic cranial pachymeningitis was based on neuroimaging findings of thickened enhancing dura, exclusion of known causes and histopathologic findings compatible with nonspecific inflammation in the meningeal biopsies. Corticosteroid therapy was effective in all cases in inducing a complete or partial remission of the neurologic symptoms and signs. We describe the clinical, radiological and pathological features of idiopathic hypertrophic cranial pachymeningitis and discuss the relationship of this entity with other inflammatory fibrosclerotic disorders to explain the pathogenesis. A high index of suspicion, prompt confirmation of the diagnosis by meningeal biopsy, and early institution and long-term maintenance of steroid therapy may help to prevent irreversible neurologic sequelae, especially blindness.     

Atypical meningioma: a clinicopathological analysis

In this retrospective study, 382 operated cases of meningiomas were reviewed. 32 cases (8.3%) were histopathologically classified as atypical meningioma. The anatomical locations and histological features in all the thirty-two cases were correlated with their recurrence rates and biological behaviour. The overall recurrence rate for atypical meningioma within two years was 28% as compared to 9.3% in benign meningiomas. It is being emphasized that an accurate histopathological interpretation of atypical meningioma is essential for predicting the recurrence, biological behavior as well as post-operative management modalities.     

The analgesic and anti-inflammatory effects of Portulaca oleracea L. subsp. Sativa (Haw.) Celak

Many ethnic groups have used different species of Portulaca oleracea L., a member of the Family Portulacaceae, as vegetable and also herbal medicine against several diseases for many centuries. A review of the records in both folkloric and scientific literature indicates that Portulaca has many medicinal uses. After our previous preliminary screening of three species of the family for analgesic and anti-inflammatory properties, Portulaca oleracea L. subsp. sativa (Haw.) Celak. (a cultivar) was chosen for further work due to its abundant availability from reliable sources. The 10% ethanolic extract of the aerial parts (dried leaves and stem) showed significant anti-inflammatory and analgesic after intraperitoneal and topical but not oral administration when compared with the synthetic drug, diclofenac sodium as the active control. Results indicate this cultivar species of Portulaca also possesses some of the claimed traditional uses of the wild species in the relief of pain and inflammation.     

Hypoplastic right ventricle with mild pulmonary stenosis in an adult.

A rare cyanotic heart disease surviving to adulthood with minimal symptoms is presented. The final diagnosis was hypoplastic right ventricle with mild pulmonary stenosis, where the latter was not responsible for the right-to-left shunting across a large atrial septal defect. The differences from cases reported in the literature are highlighted.