Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.

Rectal carcinoma in a young female patient with peutz-jeghers syndrome: a case report

To report a case of rectal cancer in a patient with Peutz-Jeghers syndrome [PJS]. A 20-year-old woman with intermittent bloody stool of 4 months was admitted for examination. Gastroendoscopy revealed multiple polyps involving the stomach, small intestine, colon and a rectal adenocarcinoma. A diagnosis of PJS was made based on intestinal polyps with characteristic pathology and melanotic macules on the lips. After surgery and chemotherapy upon follow-up at 8 months, the patient did not have any signs of recurrence. This case showed that rectal carcinoma should be considered for young patients with PJS

Genetic variations of EBV-LMP1 from nasopharyngeal carcinoma biopsies: potential loss of T cell epitopes

To find Epstein-Barr virus (EBV) strains with genetic variations of EBV latent membrane protein 1 (EBV-LMP1) from nasopharyngeal carcinoma (NPC), the full-length DNA of LMP1 genes from 21 NPC biopsies obtained in Hunan province in southern China was amplified and sequenced. Our sequences were compared to those previously reported by the Clustal V method. Results showed that all 21 sequences displayed two amino acid changes most frequently in LMP1 of CD4+ T cell epitopes at codons 144 (F arrow right I, 21/21) and 212 (G arrow right S, 19/21) or (G arrow right N, 2/21). We also show that type A EBV strain is prevalent in the cases of NPC from Hunan province with a 30-bp 18/21 deletion, and we highlight that this deletion resulted in loss of one of the CD4+ T cell-restricted epitopes. The other 3 sequences without this deletion all had a change at codon 344 (G arrow right D). Furthermore, in the major epitope sequence of CD8+ T cells restricted by HLA-A2, all 21 sequences showed changes at codons 126 (L arrow right F) and 129 (M arrow right I). Our study discovered that one of the 21 sequence variations harbored a new change at codon 131 (W arrow right C), and 5/21 specimens showed another novel change at codon 115 (G arrow right A) in the major epitope sequence of CD8+ T cells restricted by HLA-A2. Our study suggests that these sequence variations of NPC-derived LMP1 may lead to a potential escape from host cell immune recognition, protecting latent EBV infection and causing an increase in tumorigenicity.

Undernutrition during suckling has no effect on the rat locomotor activity response to caffeine

It is known that early malnutrition causes hyposensitivity to serotonergic, gabaergic, catecholaminergic and opioid stimulation. In the present study, we determined whether adult rats undernourished during suckling presented an altered response to caffeine admninistration in a locomotor actiovityyy test. Rats were undernourished during suckling by feeding their dams a 7% casein diet. During the same period, well-nourished dams were fed a 28% casein diet. Animals (90-100 days of age) were habituated to the apparatus. Thereaftert, a dose-response curve for caffeine (2.5, 10.0, 20.0, 40.0 and 120.0 umol/kg, ip) was determined. During handling sessions, undernourished rats presented lower activity scores than well-nourished animals (average values 44.2 ñ 16.4 vs 57.9 ñ 15.4). Well-nourished and undernourished rats responded in a similar way to caffeine administration by increasing the locomotor activity in a dose-dependent manner. Although undernourished animals present an altered sensitivity to various neuropharmacological compounds, the present results indicate that their sensitivity to the locomotor-actiivating effect of caffeine is the same as that of rats well-nourished during suckling

Effect of post-training injections of flumazenil into the amygdala, hippocampus and septum on retention of habituation and of inhibitory avoidance in rats

Adult rats were submitted to two different behavioral tasks using the same apparantus: the habituation of exploration of the apparatus considered as a novel environment as measured by the decrease in number of reaings and of ambulation between training and testing, and step-down inhibitory avoidance as measured by the increase in the latency to step down from a start platform into an electrified grid between the training and the test session.The training-test interval for both tasks was 20 h.The immediate post-training injection of the benzodiazepine receptor antagonist flumazenil (10 nmol) bilateral into the hippocampus enhanced retention of the two tasks.Application of the same drug, at the same dose to the septum or amygdala had no effect on habituation but enhanced retention of the avoidance task. The data are consistent with previous findings showing that both tasks are accompanied by the release of benzodiazepine like immunoreactivity in the three structures and that this release is greater after the avoidance task. The present findings suggest a differential regional involvement of endogenous benzodiazepine-mediated mechanisms in memory modulation, according to the task undertaken

Biochemical and behavioral effects of intraseptal microinjection of fasciculin, an irreversible acetylcholinesterase inhibitor

We examined the effect, in rats, of an intraseptal microinjection of fasciculin (FAS), an irreversible peptide acetylcholinesterase (AChE) inhibitor, on a)AChE activity measured in septum and hippocampus, b)3H-quinuclidiny benzylate (3H-QNB) and 3H-oxotremorine (3H-OXO) binding to hippocampal cholinergic muscarinic receptors, c) 3H-flunitrazepan (3H-FNZ) binding to hippocampal benzodiazepine receptors as a control for QNB and OXO binding, d) acquisition and retention in three different behavioral paradigms, i. e., water-finding (in which there is concomitant habituation to be apparatus), step-down inhibitory avoidance, and shuttle avoidance. AChE activity in septum decreased 2 days (-66%) and 5 days (-48%) after FAS microinjection; a slight reduction (-35%) occurred in the dorsal hippocampus on day 2 (P<0.05; N=6 per group); no changes in AChE activity were observed in ventral hippocampus ion day 2 or day 5. No changes in 3H-QNB, 3H-OXO, or 3H-FNZ binding constants were demonstrable in the hippocampus either 2 or 5 days after intraseptal FAS adminstration. No changes in training or test session performance in any of the three behavioral situations were observed 2-3 days after the intraseptal microinjection of FAS. The persistent inhibition of septal AChE caused by FAS microinjection into the septum is not sufficient to induce major changes either in hippocampal cholinergic muscarinic receptors, or in the learning or retention of behaviors regulated by the septum and/or hippocampus

Long-term treatment with 2,5-hexanedione has no effect on the specific activity of some brain and liver glycolytic enzymes of adult rats

Prolonged exposure to hexacarbon compounds is neurotoxic to humans and animals. As various hexacarbon compounds inhibit glycolytic enzymes in vitro, it has been suggested that this may underlie their neurotoxic effects in vivo. in the present investigation we examined whether long-term treatment with 2,5-hexanedione (200 mg/kg, sc) for 40 days affects the specific activity of brain and liver enolase, lactic dehydrogenase and malate dehydrogenase in female Wistar rats (150-170 g). Glycemia and liver glycogen levels were also determined. The specific activity of all enzymes tested, liver glycogen content and glycemia were not affected by chronic treatment with 2,5-hexanedione. Rats treated with 2,5-hexanedione weighed significantly less than control rats starting on day 18 of treatment (183 ñ 3.4G for the vehicle groups vs 171 ñ 3.2G for the 2,5-hexanedione group). 2,5-hexanedione also increased water intake (46 por cento when compared to vehicle-treated rats). prolonged treatmentof rats with the non-neurotoxic hexacarbon 1,6-hexanediol (207 mg/kg, sc) significantly increased liver glycogen content (5.9 ñ 0.6g/100g for the vehicle group vs 9.0 ñ 1.1g/100 g for the 1.6-hexanediol group) as well as food intake (44.0 ñ 1.5g 100g-1 6 days-1 for thge 1,6-hexanediol group). These results indicate that long-term treatment with 2,5-hexanedione did not alter the brain and liver glycolytic enzymes studied, liver glycogen content or glycemia but did reduce weight gain and increased water intake, whereas the administration of the reportedly non-neurotoxic hexacarbon 1,6-hexanediol has demonstrable metabolic effects

Effect of acute administration of 2,5-hexanedione on nociception in rats

Hexacarbon compounds are neurotxic to man and animals. These substance also inhibit various enzymes in vitro, including acetylcholinesterase. Since some cholinesterase inhibitor alter nociceptor we determined the effect of acute ip administration of 2,5-hexanedione on nociception in female Wistar rats (75-90 days old, 170-200g; 15-17 rats in each group) using a tail-flick apparatus. The rats were injected ip with vehicle solution (120mMNaCl containing 10 mM potassium phosphate buffer, pH 7.2) and 200, 400 or 800 mg/Kg of 2,5-hexanedione in a volume of 1 ml/Kg body weight. Tail-flick latencies were obtained 10, 30, 60 and 90 min after drug administration. All doses of 2,5-hexanedione caused antinociception (p<0.001) but the appearance and duration of the analgesia varied according to the dose of the drug. The highest dose tested (800 mg/Kg) caused analgesia from 10 to 60 min, 400 mg/Kg caused anal00 mg/Kg caused analgesia at 30 and 60 min, and 200 mg/Kg produced antinociception only at 60 min after drug injection (P < 0.05 for all the above comparisons). These results suggest that 2,5-hexanedione induces antinociception in rats. Whether this effect is mediated by a cholinergic mechanism is under inverstigation

Experimental infection of subperiodic Brugia malayi in laboratory rats with emphasis on evaluation by four techniques.

Infective larvae of subperiodic B. malayi from South Kalimantan (Borneo), Indonesia collected from laboratory-raised Ae. togoi mosquitoes after feeding on infected mongolian gerbils (Meriones unguiculatus) were inoculated subcutaneously into the groin areas of 15 SD and 36 LE rats. Blood was examined weekly by membrane filtration and thick smears starting 10 weeks post-infection. Microfilariae were found in 3 SD and 4 LE rats, the mf infection rate of 20% and 11% respectively. The prepatent period was significantly shorter in the SD rats (99-112 days) than those in the LE rats (110-153 days). The patent period was longer in the LE rats (208-703 days) than in the SD rats (236-543 days), and the mf density was similar (17.5 mf/20 c.mm blood against 16 mf/20 c.mm blood). At necropsy, 6 (3 female and 3 male) adult worms were recovered from 3 of 6 SD rats and 12 (9 female and 3 male) adult worms from 4 of 20 LE rats; all worms were found in the testes. The results of xenodiagnostic, histochemical staining and measuring spicules and protuberances, demonstrated clearly the difference between both species of Brugia. All dissected Ar. subalbatus mosquitoes exposed to B. pahangi became infected (100%), but none of those to subperiodic B. malayi were infected (0%). The mf of both species of Brugia in thick films stained with naphthol-AS-TR-phosphate showed that the excretory and anal pores of subperiodic B. malayi mf exhibited acid phosphatase activity and only a little activity was seen in other parts; while B. pahangi mf showed heavy diffuse acid phosphatase activity along the entire length of the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Implicacoes medicas e socio-economicas do tabagismo em familias de baixa renda em Sao Paulo (Capital). / Medical and socio-economic involvements of smoking in low-income families in Sao Paulo (Capital)

Foi realizada uma pesquisa entre as puerperas de duas maternidades de Sao Paulo, procurando-se determinar algumas implicacoes medicas e socio-economicas do tabagismo em familias de baixa renda. Concluiu-se que uma parcela significativa do orcamento familiar e destinada ao tabagismo (media de 9,8%), sendo superior as fatias orcamentarias destinadas aos gastos com transporte (media 5,8%) e com a compra de leite (media de 8,3%)

The occurrence of Candida in hospital patients and normal subjects.

The distribution of different Candida species and different serogroups of C. albicans have been analysed. C. albicans is by far the most predominant species isolated from all clinical specimens. Group A of C. albicans was isolated 10 times more frequently than group B strains from patients who had respiratory infection and 4.4 times more frequently from those who had other clinical conditions. However, both serogroups were isolated at comparable frequencies from the genitals. In the instances where repeated isolation were made, colonization by one serogroup often occurs to the exclusion of the other serogroup and species. Thus, it was frequently observed that individual patients often gave repeated isolation of one serogroup of C. albicans only. These findings are of obvious diagnostic relevance and may facilitate the evaluation of possible clinical significance of laboratory studies.