温热治疗肿瘤的基础研究进展

在肿瘤治疗学中,温热治疗是指运用不同方法对恶性肿瘤进行热治疗,他常与放疗、化疗联用,肿瘤的温度常在40-43℃．现综述温热治疗的细胞死亡、体内温热治疗的特征以及温热治疗的效应器等方面的研究进展．     

Reestablishment of the hyperglycemia to the normal levels seems not to be essential to the anxiolytic-like effect induced by insulin

Diabetes is a chronic metabolic disease accompanied by several comorbidities, including neuropsychiatric conditions. Since the hyperglycemia appears to be the primary factor involved in diabetic conditions, we examined the effect of insulin treatment in diabetic rats on behavioral responses related to anxiety and aversive memory extinction. For this, normoglycemic (NGL) or streptozotocin-diabetic (DBT) rats were submitted to the elevated T maze (ETM) and the contextual conditioned fear (CCF) tests. Therefore, animals were subjected to the prolonged treatment with insulin (6 IU/day, s.c.) to investigate the effect of the treatment on distinct behaviors. When anxiety-like responses such as the inhibitory avoidance (IA) on the ETM and the time of freezing in the first session of the CCF test were evaluated, our data showed a more pronounced anxiogenic-like behavior in DBT animals when compared to NGL ones. In addition, an increased freezing time was observed in DBT animals exposed to the CCF test (sessions 2 and 3) when compared to the NGL group, suggestive of an impairment in the extinction of aversive memory. Insulin treatment induced an anxiolytic-like effect when IA and freezing time (session 1) was evaluated, but did not alter the impaired extinction of aversive memory (sessions 2 and 3). To better understand the involvement of a rigorous control of glycaemia, we also investigated the effect of a lower dose of insulin (3 IU/day, s.c.), unable to reestablish the hyperglycemia to the normal levels, on the same behavioral parameters. Our data show that independent of the dose of insulin, the same effects were observed when animals were evaluated in the ETM and CCF tests. However, only the highest dose of insulin was able to reduce the hyperglycemia to the normal levels. To conclude, our data suggest that a severe glycemic control by insulin treatment seems to be important, but not essential in improving diabetes-induced anxiety.     

Modafinil Prevents Inhibitory Avoidance Memory Deficit Induced by Sleep Deprivation in Rats

Study Objectives:

Evaluation of modafinil effects on the inhibitory avoidance task (IA).

Design:

Rats were trained on a multiple trial IA task after receiving modafinil or vehicle injections. In experiment 1 they were trained with a weak protocol under baseline condition and in experiment 2, with a stronger protocol under sleep-deprivation condition.

Results:

In experiment 1 modafinil improved rats'' acquisition whereas the retention test remained unaffected. In Experiment 2 modafinil did not interfere with training performance, but the lower dose prevented the retention impairment in sleep-deprived animals.

Conclusions:

Modafinil is able to improve acquisition in normal rats and reverse the long-term memory impairment induced by sleep-deprivation.

Citation:

Moreira KM; Ferreira TL; Hipolide DC; Fornari RV; Tufik S; Oliveira MGM. Modafinil prevents inhibitory avoidance memory deficit induced by sleep deprivation in rats. SLEEP 2010;33(7):990-993.     

Putrescine analogue cytotoxicity against Trypanosoma cruzi

Trypanosoma cruzi is the etiological agent of American trypanosomiasis. Most of the available data on trypanosomatid parasites were obtained from African trypanosomes. Parasitic protozoa polyamine metabolism and transport pathways comprise valuable targets for chemotherapy. T. cruzi cannot synthesize putrescine, but its uptake from the extracellular milieu can promote parasite survival. Nevertheless, little is known about the cell biology of this diamine in T. cruzi. Here we notice that the putrescine analogue 1,4-diamino-2-butanone (DAB) inhibited T. cruzi epimastigotes' in vitro proliferation and produced remarkable mitochondrial destruction and cell architecture disorganization, as assessed by transmission electron microscopy. Mitochondrial damage was confirmed by MTT reduction. We decided to analyze the oxidative stress undergone by DAB-treated parasites. Thiobarbituric-acid-reactive substances were measured to assess lipid peroxidation. Analogue effects were dose-dependent; 5 mM DAB only slightly enhanced peroxidation, whereas 10 mM DAB significantly (P<0.05) diminished it. These data indicate that putrescine uptake by this diamine auxotrophic parasite may be important for epimastigote axenic growth and cellular organization.     

XPC polymorphisms play a role in tissue-specific carcinogenesis: a meta-analysis

XPC participates in the initial recognition of DNA damage during the DNA nucleotide excision repair process in global genomic repair. Polymorphisms in XPC gene have been analyzed in case-control studies to assess the cancer risk attributed to these variants, but results are conflicting. To clarify the impact of XPC polymorphisms in cancer risk, we performed a meta-analysis that included 33 published case-control studies. Polymorphisms analyzed were Lys939Gln and Ala499Val. The overall summary odds ratio (OR) for the associations of the 939Gln/Gln genotype with risk of cancer was 1.01 (95% confidence interval (95% CI): 0.94-1.09), but there were statistically significant associations for lung cancer, observed for the recessive genetic model (Lys/Lys+Lys/Gln vs Gln/Gln), (OR 1.30; 95% CI: 1.113-1.53), whereas for breast cancer a reduced but nonsignificant risk was observed for the same model (OR 0.87; 95% CI: 0.74-1.01). The results for Ala499Val showed a significant overall increase in cancer risk (OR 1.15; 95% CI: 1.02-1.31), and for bladder cancer in both the simple genetic model (Ala/Ala vs Val/Val) (OR 1.30; 95% CI: 1.04-1.61) and the recessive genetic model (Ala/Ala+Ala/Val vs Val/Val) (OR 1.32; 95% CI: 1.06-1.63). Our meta-analysis supports that polymorphisms in XPC may represent low-penetrance susceptibility gene variants for breast, bladder, head and neck, and lung cancer. XPC is a good candidate for large-scale epidemiological case-control studies that may lead to improvement in the management of highly prevalent cancers.     

ABO blood group in Amerindians from Brazilian Amazon

BACKGROUND: The Parakan? is a group of Indians with cultural similarities to the extinct Tupi group. They are an isolated native population from East Brazilian Amazon. A number of different O alleles have been found at the blood group ABO locus in populations of several ethnic origins (Caucasians, Blacks, Amerindians). AIM: The present study describes the ABO blood group polymorphism gene of the Parakan? Indians. The Amerindian group was carefully selected for racial background. SUBJECT AND METHODS: The blood group polymorphism was analysed in genomic DNA from 62 Parakan? Indians. We determined the 261G deletion, the T646A and C771T mutations described in O(1variant) and the G542A substitution, using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). RESULTS: All Amerindians studied were homozygous for the 261G deletion. The frequencies of the T646A and C771T mutations in Parakan?s (0.65) were lower than that observed in Kayapo, Yanomama and Arara Indians (0.91) (chi (2) = 18.24; p-v < 0.001. The G542A substitution in Parakan?s was also lower (0.22) than in other tribes (0.42) (chi(2) = 9.73; p-v = 0.001). CONCLUSIONS: The different O alleles including the G542A mutation are not distributed homogeneously among all Amazonian Amerindians. Our results are in agreement with other genetic markers studied previously in Parakan? Indians, whose distinct genetic pattern differs from Europeans and even from other Amerindians.     

Portable lead analyzer to locate source of lead

Objective :To investigate the sources of lead in the environment in children with elevated blood, with the help of a Field Portable X-Ray Fluorescence Analyzer.Methods : One hundred and seven school children were chosen for this study on a random basis, from Mangalore and Karnataka. Their blood lead was analyzed. Of the cases analyzed, 10 students whose blood lead level was more than 40 μg/dl were investigated using a field portable X-Ray Fluorescence Analyzer. This is the first time such a device has been available for this purpose in India.Results: The ‘likely’ source of lead exposure could be determined in eight cases which was from the immediate environment of the children like ‘lead-based’ paint on surfaces in the house, on playground and other exterior equipment; lead storage batteries, contaminated dust and soil and other lead-containing substances.Conclusion: The use of an X-Ray Fluorescence Analyser appeared to be useful in determining the source of lead     

Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure.

The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high-grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (+/- 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (+/-2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6-mo period.     

Antimicrobial resistance of Salmonella serotypes isolated from slaughter-age pigs and environmental samples

The aim of this study was to determine the antimicrobial resistance patterns of Salmonella strains isolated from slaughter-age pigs and environmental samples collected at modern swine raising facilities in Brazil. Seventeen isolates of six serotypes of Salmonella enterica subsp. enterica were isolated out of 1,026 collected samples: Salmonella Typhimurium (1), Salmonella Agona (5), Salmonella Sandiego (5), Salmonella Rissen (1), Salmonella Senftenberg (4), and Salmonella Javiana (1). Resistance patterns were determined to extended-spectrum penicillin (ampicillin), broad-spectrum cephalosporins (cefotaxime and ceftriaxone), aminoglycosides (streptomycin, neomycin, gentamicin, amikacin, and tobramycin), narrow-spectrum quinolone (nalidixic acid), broad-spectrum quinolone (ciprofloxacin and norfloxacin), tetracycline, trimethoprim, and chloramphenicol. Antimicrobial resistance patterns varied among serotypes, but isolates from a single serotype consistently showed the same resistance profile. All isolates were resistant to tetracycline, streptomycin, and nalidixic acid. One isolate, Salmonella Rissen, was also resistant to cefotaxime and tobramycin. All serotypes were susceptible to ceftriaxone, norfloxacin, ciprofloxacin, ampicillin, gentamicin, and chloramphenicol. The high resistance to tetracycline and streptomycin may be linked to their common use as therapeutic drugs on the tested farms. No relation was seen between nalidixic acid and fluoroquinolone resistance.     

Stimulation of β-adrenoceptors inhibits store-operated channel currents via a cAMP-dependent protein kinase mechanism in rabbit portal vein myocytes

Previously we have described the properties of store-operated channel currents (SOCs) in freshly dispersed rabbit portal vein smooth muscle cells. In addition to Ca²⁺ store depletion these SOCs could also be activated by α-adrenoceptor stimulation and diacylglycerol (DAG) via a protein kinase C (PKC)-dependent mechanism. In the present study we have investigated the effect of β-adrenoceptor stimulation on SOCs in rabbit portal vein myocytes. With whole-cell recording the selective β-adrenoceptor agonist isoprenaline reduced the current evoked by cyclopiazonic acid (CPA, sarcoplasmic/endoplasmic reticulum ATPase inhibitor) by over 85%. With cell-attached patch recording, bath application of isoprenaline produced a pronounced inhibition of SOC activity evoked by either CPA or the acetoxymethyl ester form of BAPTA (BAPTA-AM). SOC activity evoked by CPA, the DAG analogue, 1-oleoyl-acetyl- sn -glycerol (OAG) or the phorbol ester, phorbol-12,13-dibutyrate (PDBu) was also markedly inhibited by the adenylate cyclase activator, forskolin, and the cell-permeable non-hydrolysable analogue of cyclic adenosine monophosphate (cAMP), 8-Br-cAMP. With inside-out patches, bath application of PDBu evoked channel currents with similar properties to SOCs which were inhibited by over 90% by a catalytic subunit of protein kinase A (PKA) and by 8-Br-cAMP. Moreover bath application of PKA inhibitors, H-89, KT5720 and an inhibitory peptide to quiescent cell-attached or inside-out patches, activated channel currents with similar properties to SOCs. These data suggest that in rabbit portal vein myocytes, stimulation of β-adrenoceptors inhibits SOC activity via a cAMP-dependent protein kinase signal transduction cascade. In addition it is concluded that constitutive PKA activity has a profound inhibitory effect on SOC activity in this vascular preparation.