A rapid method of grouping beta-hemolytic streptococci using extemporaneous coagglutination

Extemporaneous coagglutination procedure for the serological grouping of beta-hemolytic streptococci is reported. Streptococcal group antigens were extracted with nitrous acid. 250 strains of groups A, B, C, F and G streptococci were tested with this method. An agreement of 100% was found between this method and the Lancefield capillary precipitation procedure. Extemporaneous coagglutination method was found to be rapid, reliable, easy and economical and could be adopted in any routine diagnostic laboratory.     

Combined effect of 2-deoxy-D-glucose and exercise on plasma catecholamine response.

2-Deoxy-D-glucose (2-DG) is a nonmetabolizable analogue of glucose that, by competitive inhibition of glucose utilization, produces a central neuroglucopenia and a peripheral hyperglycemia. This glucopenic agent was used to gain more insight into the combined effects of central glucopenia and exercise on plasma catecholamine response. This was carried out by comparing one group of exercising (26 m/min, 0% grade) rats injected with 2-DG (2-DG-EX; 250 mg/kg iv) with two control groups: one group of exercising rats injected with a saline solution (SAL-EX) and one group of resting rats injected with 2-DG (2-DG-RE). Significant (P less than 0.05) increases in blood glucose levels were observed 10 min after administration of 2-DG (7.2-13.8 and 7.3-12.4 mmol/l in 2-DG-EX and 2-DG-RE groups, respectively). These elevated blood glucose levels were maintained throughout the experiment in the 2-DG-RE condition but decreased in 2-DG-EX rats to levels observed in the SAL-EX group after 45 min of running (13.8-8.0 mmol/l). The combination of 2-DG-induced neuroglucopenia and exercise resulted in an additive response of norepinephrine (0.59 vs. 0.34 and 0.34 ng/ml; t = 12 min) and an amplified epinephrine response (1.4 vs. 0.37 and 0.31 ng/ml; t = 12 min) compared with the responses to each stimulus alone (2-DG-EX vs. 2-DG-RE and SAL-EX, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic factors and survival in metastatic breast cancer: A single institution experience

Background

The current retrospective study aims to identify some determinants of survival in metastatic breast cancer.

Methods

The study concerned 332 patients with synchronous (SM) or metachronous (MM) metastatic breast cancer treated between January 2000 and December 2007. Statistical comparison between subgroups of patients concerning survival was carried out employing log-rank test for the invariable analysis and Cox model for the multivariable analysis. Factors included: age group (≤50 years vs. >50; ≤70 years vs. >70; ≤35 years vs. >35), menopausal status, presentation of metastatic disease (SM vs. MM), disease free interval (DFI) (≤24 months vs. >24 months; ≤60 months vs. >60 months), performance status at diagnosis of metastatic disease (PS) (0–1 vs. >1), hormone receptors (HR), number of metastatic sites (1 site vs. >1), nature of the metastatic site (visceral vs. non visceral), first line therapy, surgery of the primary tumor (SPT), locoregional radiotherapy (LRRT) and use or not of bisphosphonates.

Results

Overall survival at 5 years was 12%. Positive prognostic factors in univariate analysis were: age ≤ 70 years, hormono-dependence of the tumor, good PS (PS 0–1), less than two metastatic sites, no visceral metastases, DFI ≥ 24 months, SPT or LRRT. In multivariate analysis, favorable independent prognostic factors included: good PS (PS 0–1), absence of visceral metastases (liver, lung, brain) and age ≤ 70 years.

Conclusion

Many of the prognostic factors in metastatic breast cancer found in our study are known in the literature but some of them, like the application of locoregional treatment (radiotherapy or surgery) and the use of bisphosphonates, need to be further investigated in randomized clinical trials.     

Middle Palaeolithic and Neolithic Occupations around Mundafan Palaeolake,Saudi Arabia: Implications for Climate Change and Human Dispersals

The Arabian Peninsula is a key region for understanding climate change and human occupation history in a marginal environment. The Mundafan palaeolake is situated in southern Saudi Arabia, in the Rub’ al-Khali (the ‘Empty Quarter’), the world’s largest sand desert. Here we report the first discoveries of Middle Palaeolithic and Neolithic archaeological sites in association with the palaeolake. We associate the human occupations with new geochronological data, and suggest the archaeological sites date to the wet periods of Marine Isotope Stage 5 and the Early Holocene. The archaeological sites indicate that humans repeatedly penetrated the ameliorated environments of the Rub’ al-Khali. The sites probably represent short-term occupations, with the Neolithic sites focused on hunting, as indicated by points and weaponry. Middle Palaeolithic assemblages at Mundafan support a lacustrine adaptive focus in Arabia. Provenancing of obsidian artifacts indicates that Neolithic groups at Mundafan had a wide wandering range, with transport of artifacts from distant sources.     

Secreted recombinant P53 protein from Pichia pastoris is a useful antigen for detection of serum p53: autoantibody in patients with advanced colorectal adenocarcinoma

The detection of P53 alteration by serological method is easier to perform, does not require tumor tissues and is of interest for patients monitoring. In this study, we described the development of a home made ELISA test based on recombinant human P53 protein produced in Pichia pastoris and used as antigen for the detection of serum p53-Abs in colorectal carcinoma patients. The human P53 was secreted as a His-tagged protein by recombinant KM71 strain (Kα21) via the peptide signal α of the Saccharomyces cerevisiae mating type gene. The recombinant P53-His was able to detect p53-Abs in 23.4 % of patients. Serum p53-Abs correlated significantly with surgical treatment (P = 0.007), relapse during follow-up (P = 0.036), depth of invasion (P = 0.036) and the level of CA19-9 (P = 0.034). Survival analysis showed that patients negative for serum p53-Abs exhibited a prolonged disease free survival period (P log rank = 0.012). In conclusion, the secreted recombinant human P53-His produced in P. pastoris seems to be a useful antigen for detection of serum p53 Abs in patients with colorectal carcinoma.     

Dimethoate Induces Kidney Dysfunction, Disrupts Membrane-Bound ATPases and Confers Cytotoxicity Through DNA Damage. Protective Effects of Vitamin E and Selenium

Dimethoate (DM) is an organophosphate insecticide widely used in agriculture and industry and has toxic effects on non-target organisms especially mammalian. However, we still know little about DM-induced kidney injury and its alleviation by natural antioxidants. In the present study, selenium (Se), vitamin E, DM, Se+DM, vitamin E+DM, Se+vitamin E+DM were given to adult rats for 4 weeks. Plasma creatinine and uric acid, kidney MDA, PC, H₂O₂ and AOPP levels were higher, while Na⁺-K⁺-ATPase and LDH values were lower in the DM group than those of controls. A smear without ladder formation on agarose gel was shown in the DM group, indicating random DNA degradation and DM-induced genotoxicity. A decrease in kidney GSH, NPSH and plasma urea levels and an increase in GPx, SOD and catalase activities were observed in the DM group when compared to those of controls. Plasma cystatin C levels increased, indicating a decrease in glomerular filtration rate. When Se or vitamin E was added through diet, the biochemical parameters cited above were partially restored in Se+DM and vitamin E+DM than DM group. The joint effect of Se and vitamin E was more powerful against DM-induced oxidative stress and kidney dysfunction. The changes in biochemical parameters were substantiated by histological data. In conclusion, our results indicated a possible mechanism of DM-induced nephrotoxicity, where renal genotoxicity was noted, membrane-bound ATPases and plasma biomarkers were disturbed. Se and vitamin E ameliorated the toxic effects of this pesticide in renal tissue suggesting their role as potential antioxidants.     

A novel series of histamine H4 receptor antagonists based on the pyrido[3,2-d]pyrimidine scaffold: Comparison of hERG binding and target residence time with PF-3893787

In this work we describe the optimization of a lead compound based on the quinazoline template to give a new series of potent pyrido[3,2-d]pyrimidines as histamine H₄ receptor antagonists. The pyrido[3,2-d]pyrimidine ligands have significantly reduced hERG binding compared to clinical stage compound PF-3893787 while showing good affinities at the human and rodent histamine receptors. The receptor residence time of several of these new compounds was determined for the human H₄R and compared with JNJ7777120 and PF-3893787. The pyrido[3,2-d]pyrimidines showed residence times lower than JNJ7777120 but comparable to the residence time of PF-3893787. Overall, the pyrido[3,2-d]pyrimidines show an excellent in vitro profile that warrants their further investigation in relevant models of human disease.     

The Iranian vole Microtus irani occurs in Lebanon (Mammalia: Rodentia)

We studied 1140 bp cytochrome b sequences of social voles from three localities in Lebanon. The results were compared with published sequences representing seven species of social voles. New sequences from Lebanon clustered with reference samples of two species: M. guentheri and M. irani. While M. guentheri was already reported for Lebanon, M. irani is a new addition to the fauna of Lebanon, and the third known record for the species. Animals were collected in two localities above Tripolis at 855 m and 1430 m a.s.l., respectively.     

Piophila megastigmata McAlpine 1978 (Diptera: Piophilidae): the first record from northern Africa of this forensically relevant fly

Piophila megastigmata McAlpine (Diptera: Piophilidae) is recorded for the first time from Algeria, northern Africa. This is the first Palaearctic record of the species outside the Iberian Peninsula, and the only record from Africa apart from its type locality in eastern South Africa. The current report extends significantly the known distribution in the Palaearctic Region of a species of forensic interest and of potential economic importance as a food pest.     

Inverse identification of local stiffness across ascending thoracic aortic aneurysms

Biomechanics and Modeling in Mechanobiology - Aortic dissection is the most common catastrophe of the thoracic aorta, with a very high rate of mortality. Type A dissection is often associated with...