Aktivnosti izoenzima laktat dehidrogenaze i učinci na slezenu štakora tretiranih tomilom

The toxic effect of methomyl was studied in rats after a single or repeated oral administration. Rats treated with a single dose of methomyl (3, 5, or 7 mg/kg) showed significant increase (P<0.05) in total lactate dehydrogenase activity on day 1. The highest level of LDH activity was observed on day 3 in rats receiving 7 mg/kg of methomyl. The total LDH activity returned to normal on day 7 after dosing. Specific increases in LDH-3 and LDH-4 isoenzyme activities were observed. In rats treated with a single dose of 6 and 8 mg/kg of methomyl, spleen weight and splenocyte viability significantly dropped (P<0.05) on days 1 and 3, respectively. Splenotoxicity was prevented by pretreatment with 60 mg/kg of N-acetylcysteine. The results suggest that the splenotoxic effect of methomyl is more likely directly related to oxidative cell injury than to cholinesterase inhibition. The significance of cytotoxic effects and the nature of cytotoxicity in relation to reactive oxidative damage deserve further investigation.Istraživani su učinci karbamatnog insekticida metomila u štakora. Nakon jednokratne peroralne doze od 3, 5 ili 7 mg/kg nađeno je značajno povećanje sveukupne aktivnosti laktat dehidrogenaze (LDH) nakon prvog dana tretmana. Najveća je aktivnost utvrđena trećeg dana nakon tretmana metomilom u dozi od 7 mg/kg. Enzimska aktivnost postepeno se smanjivala i sedmoga se dana normalizirala. Posebno je zapaženo povećanje aktivnosti izoenzima LDH-3 i LDH-4. U posebnim je pokusima utvrđeno značajno smanjenje težine slezene i vijabilnosti splenocita u štakora tretiranih sa 6 mg/kg i 8 mg/kg metomila i to nakon prvog i nakon trećeg dana tretmana. Toksični učinci na slezenu mogli su se spriječiti pretretiranjem sa 60 mg/kg N-acetilcisteina. Prema rezultatima ovih pokusa čini se da bi toksični učinak metomila na slezenu mogao biti izravan učinak metomila na stanice slezene a ne putem kolinergičnog mehanizma. Važnost ovakvog citotoksičnog učinka i mehanizme citotoksičnosti i njihove povezanosti s reaktivnim oksidativnim procesima pri staničnom oštećenju valja još istraživati

Association of HLA-B*5701 genotypes and abacavir-induced hypersensitivity reaction: a sysyematic review and meta-analysis

OBJECTIVES: This study aimed to systematically review and quantitatively synthesize the association between HLA-B*5701 and abacavir-induced hypersensitivity reaction (ABC-HSR). METHODS: We searched for studies that investigated the association between HLA-B genotype and ABCHSR and provided information about the frequency of carriers of HLA-B genotypes among cases and controls. We then performed a meta-analysis with a random-effects model to pool the data and to investigate the sources of heterogeneity. RESULTS: From 1,026 articles identified, ten studies were included. Five using clinical manifestation as their diagnostic criteria, 409 and 1,883 subjects were included as cases and controls. Overall OR was 23.6 (95% CI = 15.4 – 36.3). Whereas, the another five studies using confirmed immunologic test as their diagnostic criteria, 110 and 1,968 subjects were included as cases and controls, respectively. The association of ABC-HSR was strong in this populations with HLA-B*5701. Overall OR was 1,056.2 (95% CI = 345.0 – 3,233.3). CONCLUSIONS: Using meta-analysis technique, the association between HLA-B*5701 and ABC-HSR is strong in the studies using immunologic confirmation to identify ABC-HSR. These results support the US FDA recommendations for screening HLA-B*5701 allele before initiating abacavir therapy

Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson Syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

IMPORTANCE: The US Food and Drug Administration recommends screening for the HLA-B*1502 allele before initiation of carbamazepine therapy in patients of Asian ancestry, but there remains unclear evidence of a relationship between HLA-B*1502 and Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) among carbamazepine users, especially in some racial/ethnic populations. OBJECTIVE: To determine the relationship between the HLA-B*1502 allele and carbamazepine-induced SJS and TEN. DATA SOURCES: A comprehensive search of the following data sources was performed without language restriction from the inception of the database until January 8, 2013: EMBASE, PubMed, clinicaltrials.gov, Cochrane Library, IPA (International Pharmaceutical Abstracts), HuGENet (Human Genome Epidemiology Network), and CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the reference lists of identified studies. STUDY SELECTION: Inclusion criteria were studies that investigated the relationship between HLA-B*1502 and carbamazepine-induced SJS and TEN and that reported sufficient data for calculating the frequency of HLA-B*1502 carriers among cases and controls. The search yielded 525 articles, of which 16 met the inclusion criteria. The studies included 227 SJS or TEN cases, 602 matched control subjects, and 2949 population control subjects. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted the following data: study design, eligibility criteria, diagnostic criteria, patient demographics, genotype distribution, HLA-B genotyping technique, selection of cases and controls, dosage of carbamazepine and duration of use, and results of Hardy-Weinberg equilibrium in the control group. The Newcastle-Ottawa Scale was used to assess the quality of studies. The overall odds ratios (ORs) with corresponding 95% CIs were calculated using a random-effects model. The primary analysis was based on matched control studies. Subgroup analyses by race/ethnicity were also performed. MAIN OUTCOME AND MEASURE: The primary outcomewas carbamazepine-induced SJS and TEN. The outcome measure is given as an overall OR. RESULTS: The summary OR for the relationship between HLA-B*1502 and carbamazepine-induced SJS and TEN was 79.84 (95% CI, 28.45-224.06). Racial/ethnic subgroup analyses yielded similar findings for Han-Chinese (115.32; 18.17-732.13), Thais (54.43; 16.28-181.96), and Malaysians (221.00; 3.85-12 694.65). Among individuals of white or Japanese race/ethnicity, no patients with SJS or TEN were carriers of the HLA-B*1502 allele. CONCLUSIONS AND RELEVANCE: We found a strong relationship between the HLA-B*1502 allele and carbamazepine-induced SJS and TEN in Han-Chinese, Thai, and Malaysian populations. HLA-B*1502 screening in patients requiring carbamazepine therapy is warranted

Early leaf removal increases flower abscission in Vitis vinifera ‘Semillon’

Leaf removal was applied to Semillon vines in two different vineyards at different growth stages. Percentage fruit set and yield were reduced by leaf removal treatments. The magnitude of the reduction in yield was due to a decrease in bunch weight which was largely due to an increase in flower abscission and possibly the proportion of seedless berries and LGOs. The greatest reduction in yield was achieved when leaf removal was applied before and at the start of flowering.

Manejo do dossel vegetativo e seu efeito nos componentes de produção da videira Merlot.

A poda verde é uma prática cultural utilizada para melhorar as condições do dossel vegetativo dos vinhedos, visando a favorecer a qualidade da uva e do vinho. Nesse sentido, realizou-se este experimento entre as safras de 1993/1994 e 1996/1997, com diferentes modalidades de poda verde, num vinhedo do cv. Merlot conduzido em latada. Houve 12 tratamentos e três repetições, sendo o delineamento experimental em blocos casualizados. Os tratamentos constituíram-se da testemunha e de 11 diferentes modalidades de poda verde, ou seja, desbrota, desponta e desfolha, algumas delas em diferentes épocas do ciclo vegetativo da videira. O componente principal 1, da análise de componentes principais (ACP) feita em cada ano, separadamente, mostra que o tratamento 10 (desbrota + desponta + desfolha realizada no início da floração, eliminando-se as folhas abaixo dos cachos) discriminou-se nos quatro anos, e os tratamentos 7 (desfolha realizada 21 dias antes da colheita, eliminando-se metade das folhas abaixo dos cachos) e 6 (desfolha realizada 21 dias antes da colheita, eliminando-se as folhas abaixo dos cachos), em três deles; a ACP da média dos quatro anos também evidencia essa discriminação entre eles. Constata-se que o tratamento 10 foi um dos que tiveram intensidade de poda verde mais intensa, caracterizando-se por variáveis indicativas de plantas com vigor e produtividade mais baixos que os demais

Association of HLA-B*5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

Background: Despite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and meta-analyze the association between HLA-B*5801 allele and allopurinol-induced SJS/TEN.Methods: A comprehensive search was performed in databases including MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical Abstracts (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN were included. All studies were extracted by two independent authors. The primary analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol-induced SJS/TEN cases and each comparative group. The pooled odds ratios were calculated using a random effect model.Results: A total of 4 studies with 55 SJS/TEN cases and 678 matched-controls (allopurinol-tolerant control) was identified, while 5 studies with 69 SJS/TEN cases and 3378 population-controls (general population) were found. SJS/TEN cases were found to be significantly associated with HLA-B*5801 allele in both groups of studies with matched-control (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI 41.51-151.35, p < 0.001). Subgroup analysis for Asian and Non-Asian population yielded similar findings.Conclusion: We found a strong and significant association between HLA-B*5801 and allopurinol-induced SJS/TEN. Therefore, HLA-B*5801 allele screening may be considered in patients who will be treated with allopurinol

The Role of Transporters in the Pharmacokinetics of Orally Administered Drugs

Drug transporters are recognized as key players in the processes of drug absorption, distribution, metabolism, and elimination. The localization of uptake and efflux transporters in organs responsible for drug biotransformation and excretion gives transporter proteins a unique gatekeeper function in controlling drug access to metabolizing enzymes and excretory pathways. This review seeks to discuss the influence intestinal and hepatic drug transporters have on pharmacokinetic parameters, including bioavailability, exposure, clearance, volume of distribution, and half-life, for orally dosed drugs. This review also describes in detail the Biopharmaceutics Drug Disposition Classification System (BDDCS) and explains how many of the effects drug transporters exert on oral drug pharmacokinetic parameters can be predicted by this classification scheme