Hepatoprotective Activity of Heptoplus on Isoniazid and Rifampicin Induced Liver Damage in Rats

The present study is designed to evaluate the efficacy of heptoplus a polyherbal formulation as an oral supplementary agent for isoniazid and rifampicin induced hepatotoxicity in rats. 50 and 100 mg/kg of heptoplus supplement were fed orally to the rats along with isoniazid and rifampicin and compared to rats treated with 100 mg/kg Liv 52 standard drug. Rats treated with isoniazid and rifampicin suffered from severe oxidative stress by the virtue of free radicals induced lipid per oxidation. As a result abnormal index of serum biochemical markers for liver function and increased liver lysosomal enzymes activity was observed. However rats nourished with 100 mg/kg of heptoplus and Liv 52 protected the liver from oxidative damage by maintaining normal antioxidant profile status and restored normal serum liver biochemical markers. Increased liver lysosomal enzymes activity is prevented in the rats supplemented with heptoplus and Liv 52. Histopathological analysis also revealed severe vascular changes and lobular necrosis in the treatment of isoniazid and rifampicin. Heptoplus (100 mg/kg) and Liv 52 supplemented rats liver apparently revealed normal architecture of liver. This study confirms that heptoplus has liver protective activity against Isoniazid and Rifampicin induced liver injury in rats, in par with Liv 52.     

Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens

Journal of Thrombosis and Thrombolysis - Tirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic...     

Serum matrix metalloproteinase 3 levels during treatment with sulfasalazine or combination of methotrexate and sulfasalazine in patients with early rheumatoid arthritis

OBJECTIVE: To determine the effects of treatment with sulfasalazine (SSZ) or the combination of methotrexate (MTX) and SSZ on serum matrix metalloproteinase 3 (MMP-3) levels in patients with early rheumatoid arthritis (RA). METHODS: Eighty-two patients with early RA (symptoms < 1 year and DMARD-naive at presentation) were selected who had been treated with SSZ (2000 mg/day) or with the combination of MTX (7.5-15 mg/week) and SSZ. Serum MMP-3 levels, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), swollen joint count (SJC), tender joint count (TJC), Ritchie articular index (RAI), and the Disease Activity Score (DAS) were determined at 4 week intervals during a followup of 28 weeks for each treatment group. Response was based on clinical grounds and CRP at 12, 20, and 28 weeks. RESULTS: SSZ responders (n = 52) had lower baseline values of serum MMP-3, CRP, and ESR, compared to partial/nonresponders (n = 30), but did not differ in joint scores and DAS. In the SSZ responder group all variables decreased. In the SSZ partial/nonresponders, CRP, ESR, and SJC decreased in contrast to serum MMP-3, TJC. RAI, and DAS-3. After addition of MTX all variables decreased in 24 of the 30 patients who had shown a partial or no response taking SSZ. In the SSZ responders there was a delayed decrease in serum MMP-3 compared to CRP. CONCLUSION: Serum MMP-3 levels decrease in patients with early RA who respond to SSZ or to the combination of MTX and SSZ. In patients who respond to SSZ the changes in serum MMP-3 levels indicate a delayed response compared to CRP.     

Plasma therapy in thrombotic thrombocytopenic purpura: review of the literature and the Bern experience in a subgroup of patients with severe acquired ADAMTS-13 deficiency

Based on clinical studies daily plasma exchange (PE) has become the first-choice therapy for thrombotic thrombocytopenic purpura (TTP) since 1991. Recent findings may explain its effectiveness, which particularly may include supply of ADAMTS-13 and removal of anti-ADAMTS-13 autoantibodies and unusually large von Willebrand factor (VWF) multimers. The most preferable PE regimens as well as replacement fluids are discussed and treatment-related adverse reactions are summarized. Proposals for a potential reduction of their frequency and for improvement of treatment efficiency are given. These suggestions are partially based on the experience of our institution in adult patients with severe ADAMTS-13 deficiency (<5% activity), and include (1) continuous calcium-gluconate infusion during PE in order to reduce citrate-related adverse reactions; (2) the evaluation of solvent/detergent-treated (S/D) plasma as replacement fluid in order to reduce adverse events due to fresh frozen plasma (FFP); (3) the evaluation of immunoadsorption in order to increase procedural efficiency in autoantibody removal; and (4) the substitution of ADAMTS-13 by means of recombinant drug instead of plasma.     

von Willebrand factor-cleaving protease (ADAMTS-13) activity determination in the diagnosis of thrombotic microangiopathies: the Swiss experience

Severe deficiency of von Willebrand factor (VWF)-cleaving protease (ADAMTS-13) activity (<5% of normal) is a specific finding for acute idiopathic thrombotic thrombocytopenic purpura (TTP), a disorder that presents as thrombocytopenia, microangiopathic hemolytic anemia, and often organ dysfunction such as neurological disturbances or renal failure, and fever. Between January 2001 and July 2003, ADAMTS-13 activity was determined in plasma samples of 396 consecutive patients referred to our laboratory for diagnostic purposes. Plasma samples with ADAMTS-13 activity less than 5% were in addition tested for the presence of inhibitory antibodies. Patients were assigned to 10 predefined clinical categories according to information provided by the referring clinician: thrombotic microangiopathy (TMA) not further specified; neoplasia- or chemotherapy-associated TMA; TMA following hematopoietic stem cell transplantation; TMA with additional/alternative disorder; idiopathic TTP; hemolytic-uremic syndrome (HUS) not specified; HUS with diarrhea prodrome (D+HUS); atypical HUS; other hematological disorder; and no clinical information available. Severe ADAMTS-13 deficiency was found in 69 (17%) patients, including 42 with acquired idiopathic TTP, either at initial presentation or at relapse, 14 with confirmed or suspected hereditary TTP, 10 with TMA not further specified, two with neoplasia- or chemotherapy-associated TMA, and one in continued clinical remission 3.4 years after splenectomy for plasma-refractory TTP. Forty-three (62%) patients with ADAMTS-13 activity less than 5% displayed inhibitory antibodies. Severe ADAMTS-13 deficiency was found in 60% of patients diagnosed with acute idiopathic TTP, but in none of 130 patients diagnosed with HUS or in any of the 14 patients with hematopoietic stem cell transplantation-associated TMA. Thus, plasma ADAMTS-13 activity less than 5% does not identify all patients clinically diagnosed with TTP, and severe ADAMTS-13 deficiency is not invariably associated with clinical manifestations of microvascular platelet clumping.     

Plasma volume and blood pressure regulation in hypertensive pregnancy.

BACKGROUND: Pre-eclampsia is a multisystem disorder, peculiar to and frequent in human pregnancy. It remains a leading cause of maternal and neonatal morbidity and mortality. Hemodynamic disturbances are the most prominent features of the syndrome. PURPOSE: To provide an overview of plasma volume regulation and blood pressure control mechanisms outside pregnancy, and of the changes in normal pregnancies and in pregnancies complicated by hypertensive disorders. Furthermore, to discuss the rationale of several hemodynamic interventions. RESULTS: In normal pregnancy, large cardiovascular changes take place. A generalized fall in vascular tone by systemic vasorelaxation causes increased blood volume, heart rate and cardiac output. In the preclinical phase, differences have been observed between normal and hypertensive pregnancies in the function of the autonomic nervous system, cardiac output and plasma volume, the volume remaining at the non-pregnant level. In the clinical phase of pre-eclampsia the typical case picture is one of a vasoconstrictive state with low plasma volume and cardiac output, high blood pressure and systemic vascular resistance in combination with signs of organ damage [proteinuria, hemolysis elevated liver enzymes low platelets (HELLP) syndrome]. Hemodynamic management is necessary in severe disease to prevent maternal complications. Management primarily focuses on pharmacological treatment of blood pressure. Clinicians make educated choices from a limited array of available drugs: beta-receptor antagonists, nifedipine, dihydralazine, methyldopa or ketanserine. Other drugs have restricted use in pregnancy. Management of low circulating volume with plasma expanders remains a subject of controversy.