Long-term treatment with an ACE inhibitor or an AT1 antagonist avoids hypertension-induced inflammation in the kidney

BACKGROUND: Hypertension causes an inflammatory response in the kidney. Many studies have demonstrated that activation of the renal renin-angiotensin system, and therefore an increase in local angiotensin II (AngII) production, participates in the renal inflammatory cell recruitment. Our aim was to investigate the role of AngII blockade in hypertension-induced inflammatory response. METHODS: To replicate chronic hypertension with renal disease, we used a model of spontaneously hypertensive rats with unilateral nephrectomy (UNX-SHR). These animals were studied for 48 weeks. We investigated the effect of long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II type 1 (AT1 ) antagonist, 2 strategies currently used in humans, on renal proinflammatory parameters. RESULTS:UNX-SHR rats presented elevated renal inflammatory cell infiltration and up-regulation of proinflammatory factors, including activation of nuclear factor chi B (NF-chi B) and related genes. Both ACE inhibition and AT 1 blockade decreased the number of inflammatory cells as well as the up-regulation of proinflammatory factors in the kidney. CONCLUSIONS: These results suggest that either AT 1 blockade or ACE inhibition can stop the renal inflammatory process in chronic hypertension-associated inflammatory response.     

Palliative goals, patient selection, and perioperative platelet management: outcomes and lessons from 3 decades of splenectomy for myelofibrosis with myeloid metaplasia at the Mayo Clinic

BACKGROUND: Although splenectomy may palliate massive splenomegaly in patients with myelofibrosis with myeloid metaplasia, this procedure carries significant risks. The authors retrospectively analyzed their experience with splenectomy over the course of 30 years to analyze the impact of improved techniques, antimicrobials, and aggressive postoperative control of platelet counts on outcome. METHODS: A total of 314 patients underwent splenectomy between 1976 and 2004 for mechanical symptoms (= 156 patients [49%]), anemia (= 78 patients [25%]), portal hypertension (= 47 patients [15%]), or thrombocytopenia (= 33 patients [11%]). Of a total of 91 patients studied during the last decade, 69 patients (76%) experienced a palliative benefit for their primary surgical indication for a median of 12 months (range, 1-91 months). RESULTS: Perioperative complications occurred in 87 patients (27.7%) including infection (= 31 patients [9.9%]), thrombosis (= 31 patients [9.9%]), or bleeding (= 44 patients [14%]), 21 of which (6.7% of all patients) were fatal. Perioperative thrombohemorrhagic complications decreased in the last decade through the use of platelet apheresis and the prompt use of cytoreductive agents to counteract postsplenectomy thrombocytosis. Survival after splenectomy was found to be decreased in patients with preoperative thrombocytopenia (<100 x 10(9)/L [P = 0.006]) but not by indication, myelofibrosis with myeloid metaplasia (MMM) prognostic score, or the decade in which splenectomy was performed. CONCLUSIONS: The lack of improvement in overall postsplenectomy survival over time may be a reflection on the failure of medical therapy to improve survival in patients with MMM.     

Reduction in the susceptibility of Aedes aegypti to Brugia malayi infection after treatment with ethyl methanesulfonate.

The susceptibility to Brugia malayi infections of F2 and F4 progenies of Aedes aegypti (Black Eye strain) treated with ethyl methanesulfonate (EMS) was tested. Both 3-day-old males and females were treated with 0.025, 0.050, 0.075 and 0.10% EMS. Control and treated females were then mated with normal or treated males to recover F1 progeny. F2 offspring were derived from sibling intercrosses, and 3 lines were established by further intercross matings to generate the F4. Susceptibility in the 0.025, 0.050, 0.075 and 0.10% EMS F2s was reduced by 13, 12, 4 and 25%, respectively. The 0.025% and 0.050% EMS F2 females showed a 29 to 39% decrease in mean L3 numbers. At 0.075 and 0.10% EMS, mean L3 numbers decreased by 0.8 and 71%, respectively. The F4 populations gave overall infections of 65, 56 and 22% for the control, 0.25 and 0.10% EMS lines, respectively. Mean L3s were reduced by 24 and 77%, respectively, in the 0.025 and 0.10% F4 EMS-selected populations.     

Digoxin and endotoxin: A lethal pro-inflammatory combination

Inflammation Research -     

The relationship between patients' satisfaction with their physicians and perceptions about interventions they desired and received

This study was designed to determine the relationship between patients' satisfaction with their physician, the types of interventions that patients reported they received, and the congruence between those interventions and the types of interventions they desired. One hundred eighteen symptomatic adult primary-care patients completed questionnaires before and after their respective medical visits. Patients who indicated they received any one of the three nontechnical interventions: education (P less than 0.001), stress counseling (P less than 0.05), and negotiation (P less than 0.01), were significantly more satisfied than those who had not received these interventions. Patient perceptions about receiving technical interventions, i.e., examination, tests, medications, and nondrug therapy, were not related to patient satisfaction. The congruence between patient-intervention desires and perceptions about interventions received generally were not significantly related to satisfaction except for the interaction between receiving a medication and postvisit-medication desires (P less than 0.001). A series of multiple regression analyses revealed that, in general, perceptions about nontechnical interventions were better predictors of patient satisfaction than perceptions about technical interventions.     

Mitochondrial encephalomyopathy and partial cytochrome c oxidase deficiency

A 52-year-old man had slowly progressive weakness and wasting of limb-muscles, sensorineural hearing loss, and complex partial seizures. CT showed cerebral atrophy, but he was not demented. Muscle biopsy showed ragged-red fibers and decreased histochemical stain for cytochrome c oxidase. Biochemical studies showed decreased cytochrome c oxidase activity in crude muscle extracts and in isolated mitochondria (44 and 30% of normal), while other mitochondrial enzymes were normal. A comparable decrease of immunologically reactive enzyme protein was shown by immunotitration with antibodies against human heart cytochrome c oxidase. Partial defects of cytochrome c oxidase may cause adult-onset, slowly progressive mitochondrial encephalomyopathies.