Characterization of salivaricin CRL 1328, a two-peptide bacteriocin produced by Lactobacillus salivarius CRL 1328 isolated from the human vagina

Salivaricin CRL 1328 is a heat-stable bacteriocin produced by Lactobacillus salivarius CRL 1328, a strain isolated from healthy human vagina, with potential applications for preventing urogenital infections. The objective of this study was to characterize the locus responsible for salivaricin CRL 1328 production and its mechanism of action against Enterococcus faecalis MP97 as the sensitive strain. Oligonucleotides were designed based on sequences of antimicrobial peptides previously described in the literature. The salivaricin CRL 1328 cluster was identified, sequenced and analyzed. This cluster was similar to the previously described ABP118 which codified for a two-peptide bacteriocin. The putative mature peptides of salivaricin CRL 1328, Salα and Salβ were chemically synthesized. These peptides did not show bacteriocin activity when assayed individually. Both peptides exhibited optimal antimicrobial activity at an equimolar ratio. Spectroscopic fluorescence assays were carried out using the synthetic peptides to study the effect of salivaricin on proton motive force. This bacteriocin was shown to dissipate membrane potential and the transmembrane proton gradient, both components of proton motive force. E. faecalis MP97 cells treated with salivaricin CRL 1328 peptides were observed in transmission electron microscopy which revealed ultrastructural modifications of the cell wall.     

Risk factors associated with the development of ischemic colitis

AIM:To ascertain the role of cardiovascular risk factors,cardiovascular diseases,standard treatments and other diseases in the development of ischemic colitis(IC).METHODS:A retrospective,case-control study was designed,using matched data and covering 161 incident cases of IC who required admission to our hospital from 1998 through 2003.IC was diagnosed on the basis of endoscopic findings and diagnostic or compatible his-tology.Controls were randomly chosen from a cohort of patients who were admitted in the same period and required a colonoscopy,excluding those with diagnosis of colitis.Cases were matched with controls(ratio 1:2),by age and sex.A conditional logistic regression was performed.RESULTS:A total of 483 patients(161 cases,322 con-trols)were included;mean age 75.67±10.03 years,55.9%women.The principal indications for colonos-copy in the control group were lower gastrointestinal hemorrhage(35.4%),anemia(33.9%),abdominal pain(19.9%)and diarrhea(9.6%).The endoscopic findings in this group were hemorrhoids(25.5%),diverticular disease(30.4%),polyps(19.9%)and colorectal cancer(10.2%).The following variables were associated with IC in the univariate analysis:arterial hypertension(P= 0.033);dyslipidemia(P<0.001);diabetes mellitus(P =0.025);peripheral arterial disease(P=0.004);heart failure(P=0.026);treatment with hypotensive drugs(P=0.023);angiotensin-converting enzyme inhibitors;(P=0.018);calcium channel antagonists(P=0.028);and acetylsalicylic acid(ASA)(P<0.001).Finally,the following variables were independently associated with the development of IC:diabetes mellitus[odds ratio(OR)1.76,95%confidence interval(CI):1.001-3.077,P=0.046];dyslipidemia(OR 2.12,95%CI:1.26-3.57,P=0.004);heart failure(OR 3.17,95%CI:1.31-7.68,P=0.01);peripheral arterial disease(OR 4.1,95%CI:1.32-12.72,P=0.015);treatment with digoxin(digitalis)(OR 0.27,95%CI:0.084-0.857,P=0.026);and ASA(OR 1.97,95%CI:1.16-3.36,P=0.012).CONCLUSION:The development of an episode of IC was independently associated with diabetes,dyslipid-emia,presence     

Cognitive vs. affective listening modes and judgments of music - An ERP study

The neural correlates of processing deviations from Western music rules are relatively well known. Less is known of the neural dynamics of top-down listening modes and affective liking judgments in relation with judgments of tonal correctness. In this study, subjects determined if tonal chord sequences sounded correct or incorrect, or if they liked them or not, while their electroencephalogram (EEG) was measured. The last chord of the sequences could be congruous with the previous context, ambiguous (unusual but still enjoyable) or harmonically inappropriate. The cognitive vs. affective listening modes were differentiated in the event-related potential (ERP) responses already before the ending chord, indicating different preparation for the judgment tasks. Furthermore, three neural events tagged the decision process preceding the behavioral responses. First, an early negativity, peaking at about 280 ms, was elicited by chord incorrectness and by disliking judgments only over the right hemisphere. Second, at about 500 ms from the end of the sequence a positive brain response was elicited by the negative answers of both tasks. Third, at about 1200 ms, a late positive potential (LPP) was elicited by the liking judgment task whereas a large negative brain response was elicited by the correctness judgment task, indexing that only at that late latency preceding the button press subjects decided how to judge the cadences. This is the first study to reveal the dissociation between neural processes occurring during affective vs. cognitive listening modes and judgments of music.     

Pachydermodactyly in a Young Girl: Cutaneous Manifestation of a Psychiatric Disorder?

Abstract: ; Pachydermodactyly is a benign process characterized by painless fusiform skin swellings affecting radial and ulnar aspects of the proximal interphalangeal joints of the fingers. We report a case of this condition in a young girl, suggesting a major role of psychiatric disorder in the development of cutaneous lesions.     

The Anatomy of the Gastrointestinal Tract of the African Lungfish,Protopterus annectens

The gastrointestinal tract of the African lungfish Protopterus annectens is a composite, which includes the gut, the spleen, and the pancreas. The gut is formed by a short oesophagus, a longitudinal stomach, a pyloric valve, a spiraling intestine, and a cloaca. Coiling of the intestine begins dorsally below the pylorus, winding down to form six complete turns before ending into the cloaca. A reticular tissue of undisclosed nature accompanies the winding of the intestinal mucosa. The spleen is located along the right side of the stomach, overlapping the cranial end of the pancreas. The pancreas occupies the shallow area, which indicates on the gut dorsal side the beginning of the intestine coiling. In addition, up to 25 lymphatic‐like nodes accompany the inner border of the spiral valve. The mesenteric artery forms a long axis for the intestine. All the components of the gastrointestinal tract are attached to each other by connective sheaths, and are wrapped by connective tissue, and by the serosa externally. We believe that several previous observations have been misinterpreted and that the anatomy of the lungfish gut is more similar among all the three lungfish genera than previously thought. Curiously, the gross anatomical organization is not modified during aestivation. We hypothesize that the absence of function is accompanied by structural modifications of the epithelium, and are currently investigating this possibility. Anat Rec 293:1146–1154, 2010. © 2010 Wiley‐Liss, Inc.     

Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantation

Abstract:  Free radicals are involved in pathophysiology of ischemia/reperfusion injury (IRI). Melatonin is a potent scavenger of reactive oxygen and nitrogen species. Thus, this study was designed to elucidate its effects in a model of rat kidney transplantation. Twenty Lewis rats were randomly divided into 2 groups (n = 10 animals each). Melatonin (50 mg/kg BW) dissolved in 5 mL milk was given to one group via gavage 2 hr before left donor nephrectomy. Controls were given the same volume of milk only. Kidney grafts were then transplanted into bilaterally nephrectomized syngeneic recipients after 24 hr of cold storage in Histidine–Tryptophan–Ketoglutarate solution. Both graft function and injury were assessed after transplantation through serum levels of blood urea nitrogen (BUN), creatinine, transaminases, and lactate dehydrogenase (LDH). Biopsies were taken to evaluate tubular damage, the enzymatic activity of superoxide dismutase (SOD) and lipid hydroperoxide (LPO), and the expression of NF-kBp65, inducible nitric oxide synthase (iNOS), caspase-3 as indices of oxidative stress, necrosis, and apoptosis, respectively. Melatonin improved survival ( P  < 0.01) while decreasing BUN, creatinine, transaminases, and LDH values up to 39–71% ( P  < 0.05). Melatonin significantly reduced the histological index for tubular damage, induced tissue enzymatic activity of SOD while reducing LPO. At the same time, melatonin down-regulated the expression of NF-kBp65, iNOS, and caspase-3. In conclusion, donor preconditioning with melatonin protected kidney donor grafts from IRI-induced renal dysfunction and tubular injury most likely through its anti-oxidative, anti-apoptotic and NF-kB inhibitory capacity.     

Risk of hypospadias in newborn infants exposed to valproic acid during the first trimester of pregnancy: a case-control study in Spain.

BACKGROUND: Hypospadias is one of the most frequently occurring genital anomalies described in infants prenatally exposed to valproic acid (VA). However, to our knowledge, only one publication has studied a potential causal relationship between VA and hypospadias, only estimating the unadjusted global risk. Here we present the results of a multivariate case-control study aimed at analysing and quantifying the specific risk of hypospadias in newborn infants exposed to VA during the first trimester of pregnancy. METHODS: The data analysed here were derived from the Spanish Collaborative Study of Congenital Malformations (ECEMC), an ongoing, hospital-based, case-control study and surveillance system in which collaborating paediatricians identify case and control infants. The paediatricians collect the same data for both case and control infants, blinded to information on any prenatal exposure. The information includes 312 items related to many prenatal exposures, including drug exposure, reproductive and family history, and other characteristics. The sample analysed included 2,393 infants with hypospadias and 12,465 male controls. RESULTS: The results showed that the unadjusted risk of hypospadias in infants prenatally exposed to VA was 5.23 (95% CI 2.31, 11.86; p < 0.00001). Once adjusted for 13 potential confounding factors using conditional logistic regression analyses, the value of the risk was of a similar magnitude (odds ratio = 5.71; 95% CI 1.78, 18.36; p = 0.003). In addition, the frequency of hypospadias in the study population was approximately 1.8/1000 births. This allowed us to calculate the specific risk for an infant with hypospadias to be born to an exposed mother, which was 1 child in 97 births to mothers using VA during the first trimester of pregnancy. We consider this information much more useful for risk assessment than the risk value itself. CONCLUSIONS: An alteration of placental gonadotrophic stimulation caused by changes in gonadotropin-releasing hormone release produced by the effects of VA on GABA is a possible pathogenic mechanism. Our results support the relationship between prenatal exposure to VA and hypospadias.     

Generalised erythematous skin eruptions induced by sorafenib: cutaneous toxicity and treatment outcome

A woman diagnosed of a renal cell carcinoma in 1989 had a metastatic kidney cancer localised in subcutaneous nodules, gut and lung in 2007. Sorafenib treatment was initiated a 400 mg orally twice a day. The patient developed generalised erythematous skin eruptions and two weeks later a widespread erythematous maculopapular eruption located exclusively on the legs and arms, along with an objective response. The most likely cause of the generalised erythematous skin eruptions was considered to be sorafenib because of the close temporal relationship between exposure to the drug and onset of symptoms. Furthermore, a relationship between sorafenib skin toxicity and treatment efficacy was observed. This therapeutic efficacy of EGFR inhibitors and cutaneous side effects should be better assessed in large cohorts or trials to determine whether the skin toxicity of patients can be linked to an objective antitumour response.     

Changes in biological markers after primary chemotherapy for breast cancers

The profiles of functional (proliferative rate and cell distribution in the cell cycle) and phenotypic (nuclear DNA content and hormone receptor status) biological markers and the expression of P53 and Bcl-2 proteins were prospectively evaluated in breast cancers before and after different regimens of primary chemotherapy. Overall, changes induced on the 2 proliferation indices (³H-thymidine labelling index, ³H-dT LI, and flow-cytometric S-phase fraction, FCM-S) mainly consisted of a decrease for rapidly proliferating tumours and an increase or no change for slowly proliferating tumours. However, when considered as a function of treatment type, changes of ³H-dT LI and FCM-S were superimposable in rapidly proliferating tumours, regardless of the type of treatment, and in slowly proliferating tumours only after anthracycline-including regimens. Conversely, following CMF, FCM-S was increased in 90% of the cases and ³H-dT LI in only 50%. Our data imply that the 2 proliferation indices could reflect different phenomena: an actual variation of proliferative activity by ³H-dT LI and an accumulation of cells in the S-phase by FCM-S. In addition, a higher accumulation of cells in G₂-M phases could be detected by FCM after anthracycline-including regimens than after CMF. The fraction of P53-positive cells was reduced by primary chemotherapy in about 50% of P53-positive tumours, whereas Bcl-2 expression was only marginally affected. DNA ploidy and hormone receptor status did not change in about 75% of cases, regardless of the chemotherapeutic regimen. © 1995 Wiley-Liss, Inc.