Bioreabsorbable polymer scaffold as temporary meniscal prosthesis

Menisci have an important role in load bearing, shock absorption, knee joint stability, and joint lubrication. Meniscal lesions and meniscectomy are followed by osteoarthritis in a high percentage of patients. At present, there is no ideal prosthesis for meniscal substitution. In this work, a bioreabsorbable polymer scaffold made of poly(L-lactic acid) (PLLA) and poly(p-dioxanone) (PPD) blend was developed to be used as a temporary meniscal prosthesis to stimulate the formation of an in situ meniscal replication while the scaffold is reabsorbed by the organism. Total meniscectomy of medial meniscus and arthrotomy was made in both back knees of 34 adult New Zealand white rabbits by medial parapatellar incision. The scaffolds were sutured in one of the knees, and other was used as a control. A meniscal replica was developed, suggesting that this material has great potential to be used as a meniscal prosthesis, especially because the new meniscus promoted a significant protection of cartilage, and cartilage degeneration in the control condyles was observed.     

Primary lymphoepithelioma-like carcinoma of the urinary bladder: Report of one case with review and update of the literature after a pooled analysis of 43 patients

Background and objectives:Lymphoepithelioma-like carcinoma (LELC) is anundifferentiated epithelial tumor with a denseinflammatory infiltrate that resembles thelymphoepithelioma of the nasopharinx occurringin other sites. Primary LELC of the bladder(LELCB) was first reported by Zukerberg et alin 1991. The incidence of LELCB is 0.4%–1.3% of all bladder carcinomas. The mean ageat diagnosis is 69 years. Of the patientpopulation 69% are men. Herein we report onone more case of primary predominant LELCB andreview all the English literature concerningthis subject after performing a pooled analysisof the cases recorded in the Eglish literatureincluding the present one.Materials and methods: The reports of 43patients including the present case of primaryLELCB from the English literature werecollected from 1991 to 2002. Patients wereevaluated for age, sex, primary and adjuvanttreatments, clinical staging, follow-up andoutcome, and disease related survival. Theoverall patient population was separated into 3groups according to the LELCB classification ofAmin. Results: The overall patientpopulation included 31 males and 12 females.Average age was 68.4 years (range 52–84). LELCBhistological subtypes resulted pure in 17cases(40%), predominant in 16 (37%) and focal in10 (23%). Mean follow-up was 37.7 months(range 0–216). Outcome resulted as follows: 26patients (62%) did not show evidence ofdiasease (62%), 11 (26%) died of disease, 1(2%) was alive with metastases, and 4 (10%)died for causes unrelated to the primarydisease. Survival rate related to specificdisease resulted 71%. Mean follow-up was 48.1in the first group (pure LELCB), 32 in thesecond (predominant LELCB), and 30.3 in thethird one (focal LELCB). Patients with notevidence of disease were 13 (81%) in group 1,13 (82%) in group 2, and 0 in group 3.Patients who died of their disease resulted 1(6%) in the first group, 1 (6%) in thesecond, and 9 (90%) in the third one. Patientswho died for disease not related to the primarytumor were 2 (13%) in the first group, 1 (6%)in the second, and 1 (10%) in the third one.One patient (6%) was alive with metastases ingroup 2. Survival rate related to specificdisease resulted 93% in the first group, 93%in the second one, and 0% in the third one.Conclusions:To date, there are no clear guide lines for the treatment of LELCB. Treatments performedinclude both deep transurethral resection ofthe tumor (TUR-B) as well as partial or radicalcystectomy, with or without adjuvant treatmentsincluding systemic chemotherapy andradiotherapy. The prognosis is favorable forpatients presenting with the pure andpredominant forms with a diploid DNA patternand very poor for patients presenting withfocal LELCB. Bladder salvage therapy byperforming both TUR-B alone or combined withadjuvant systemic chemotherapy may be areasonable option for patients with pure orpredominant LELCB, while radical surgery withadjuvant systemic therapy may be indicated forfocal muscle invasive LELCB.     

Association between smoking and paracoccidioidomycosis: a case-control study in the State of Espírito Santo,Brazil

Paracoccidioidomycosis, the main systemic mycosis in Brazil, requires long-term, high-cost treatment and leaves serious sequelae in the lungs, the organ most frequently affected and further subject to aggressive external risk factors like smoking. The influence of tobacco and alcohol consumption on chronic paracoccidioidomycosis was investigated using a case-control study. Data on occupation, place of residence, and living habits were obtained from 70 cases and 180 controls residing in the same geographic areas. The risk of becoming ill was 14 times greater among smokers and 3.6 times greater among individuals with an alcohol intake of more than 50 g/day. Logistic regression showed as significant variables: tobacco consumption for more than 20 years (OR = 10.1), smoking manufactured (not hand-rolled) cigarettes (OR = 4.8), and alcohol intake > 50 g/day (OR = 2.9). Cases who smoked 20 or more cigarettes/day became ill on average eight years before others (p = 0.002). Alcohol intake > 50 g/day had no statistically significant impact on age at onset of illness (p = 0.78). The study concludes that smoking stands as an important risk factor for the development of chronic paracoccidioidomycosis. As for alcoholism, there is evidence that it acts as a co-factor, together with smoking.     

Coronary artery anomalies: assessment with free-breathing three-dimensional coronary MR angiography

PURPOSE: To evaluate a simplified protocol by using free-breathing three-dimensional (3D) coronary magnetic resonance (MR) angiography to determine the anatomy of anomalous coronary arteries, in particular the relationship of the vessels to the aortic root. MATERIALS AND METHODS: Twenty-six patients (18 men, eight women; mean age, 50 years; age range, 18-77 years) who had a history of chest pain, palpitations, or syncope and who were suspected of having coronary artery anomalies were examined with free-breathing MR angiography. Multiple 3D volume slabs were acquired at the level of the sinuses of Valsalva by using diaphragmatic navigators for respiratory artifact suppression. The proximal anatomy of the coronary arteries was determined. RESULTS: Six anomalous circumflex arteries originated from the right sinus of Valsalva and passed behind the aortic root. Six right coronary arteries arose from the left sinus of Valsalva and coursed between the aortic root and the right ventricular outflow tract (RVOT). Nine left coronary arteries arose from the right sinus of Valsalva; seven of nine coursed between the aortic root and the RVOT. Five patients had minor anomalies. Overall, in eight patients with anomalous arteries that coursed between the aortic root and the RVOT, conventional coronary angiography could not be used confidently to identify the proximal course. CONCLUSION: Free-breathing 3D coronary MR angiography can be used to identify the proximal anatomy of anomalous coronary arteries.     

Minalrestat,an aldose reductase inhibitor,corrects the impaired microvascular reactivity in diabetes

We demonstrated that aldose reductase inhibition corrects the impaired microvascular responses to inflammatory mediators in diabetic rats. To study the mechanism involved in the restoring effect of aldose reductase inhibition, we examined the effects of minalrestat, another aldose reductase inhibitor, on the responses of mesenteric microvessels studied in vivo to permeability-increasing agents in diabetic and galactosemic rats. The diabetic group was treated from 3 days after the alloxan injection with minalrestat (10 mg/kg/day) for 30 days and the minalrestat treatment (10 mg/kg/day/7 days) of galactosemic rats started concomitantly with the induction of galactosemia. The mesenteric microvessel reactivity was studied using intravital microscopy and changes in vessel diameters were estimated after the topical application of vasoactive agents. The impaired responses to bradykinin, histamine, and platelet-activating factor of arterioles and venules observed in diabetic and galactosemic rats were completely prevented by minalrestat. Neither diabetes nor galactosemia affected responses to acetylcholine and sodium nitroprusside. Responses to these agents were not modified by aldose reductase inhibition. The restoring effect of minalrestat was reversed by inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester, by blocking K(+) channel with tetraethylammonium but not by cyclooxygenase inhibition with diclofenac. Therefore, we concluded that NO, membrane hyperpolarization, but not cyclooxygenase products are involved in the beneficial effect of minalrestat on the microvascular reactivity in diabetes. Together, these findings led us to suggest that aldose reductase inhibition might ameliorate diabetic complications through the correction of the altered microvascular reactivity by a mechanism that involves NO and membrane hyperpolarization.     

Variants in genes of innate immunity,appetite control and energy metabolism are associated with host cardiometabolic health and gut microbiota composition

ABSTRACT

Identifying the genetic and non-genetic determinants of obesity and related cardiometabolic dysfunctions is cornerstone for their prevention, treatment, and control. While genetic variants contribute to the cardiometabolic syndrome (CMS), non-genetic factors, such as the gut microbiota, also play key roles. Gut microbiota is intimately associated with CMS and its composition is heritable. However, associations between this microbial community and host genetics are understudied. We contribute filling this gap by genotyping 60 variants in 39 genes of three modules involved in CMS risk, measuring cardiometabolic risk factors, and characterizing gut microbiota in a cohort of 441 Colombians. We hypothesized that CMS risk variants were correlated with detrimental levels of clinical parameters and with the abundance of disease-associated microbes. We found several polymorphisms in genes of innate immunity, appetite control, and energy metabolism that were associated with metabolic dysregulation and microbiota composition; the associations between host genetics and cardiometabolic health were independent of the participants’ gut microbiota, and those between polymorphisms and gut microbes were independent of the CMS risk. Associations were also independent of the host genetic ancestry, diet and lifestyle. Most microbes explaining genetic-microbiota associations belonged to the families Lachnospiraceae and Ruminococcaceae. Multiple CMS risk alleles were correlated with increased abundance of beneficial microbiota, suggesting that the phenotypic outcome of the evaluated variants might depend upon the genetic background of the studied population and its environmental context. Our results provide additional evidence that the gut microbiota is under the host genetic control and present pathways of host–microbe interactions.     

TLR2- and 4-independent immunomodulatory effect of high molecular weight components from Ascaris suum

Components of high molecular-weight (PI) obtained from Ascaris suum extract down-regulate the Th1/Th2-related immune responses induced by ovalbumin (OVA)-immunization in mice. Furthermore, the PI down-modulates the ability of dendritic cells (DCs) to activate T lymphocytes by an IL-10-mediated mechanism. Here, we evaluated the role of toll like receptors 2 and 4 (TLR2 and 4) in the modulatory effect of PI on OVA-specific immune response and the PI interference on DC full activation. An inhibition of OVA-specific cellular and humoral responses were observed in wild type (WT) or in deficient in TLR2 (TLR2^−/−) or 4 (TLR4^−/−) mice immunized with OVA plus PI when compared with OVA-immunized mice. Low expression of class II MHC, CD40, CD80 and CD86 molecules was observed in lymph node (LN) cells from WT, TLR2^−/− or TLR4^−/− mice immunized with OVA plus PI compared with OVA-primed cells. We also verified that PI was able to modulate the activation of DCs derived from bone marrow of WT, TLR2^−/− or TLR4^−/− mice induced in vitro by agonists of TLRs, as observed by a decreased expression of class II MHC and costimulatory molecules and by low secretion of pro-inflammatory cytokines. Its effect was accompanied by IL-10 synthesis. In this sense, the modulatory effect of PI on specific-immune response and DC activation is independent of TLR2 or TLR4.     

Occult spinal cord abnormalities in children referred for orthopedic complaints

This study reviews spinal cord abnormalities found in children initially referred for an orthopedic problem. Over a 5-year period in an academic pediatric orthopedic referral clinic, 167 children aged 3 months to 18 years (average, 9.4 years) underwent spine magnetic resonance imaging (MRI) scans and had records available for review. The patients were divided into 7 major groups based on the primary indication for the MRI. The frequency of spinal cord pathology was as follows: 3 of 35 patients with atypical idiopathic scoliosis, 1 of 19 with neuromuscular scoliosis, 6 of 18 with congenital scoliosis, 1 of 50 with unexplained back pain, 3 of 17 with gait abnormality, 5 of 14 with limb pain or weakness, and 4 of 8 with rigid or recurrent foot deformity. Spine MRI was not very helpful in evaluating children who had some degree of back pain without neurological signs or symptoms. However, the spine MRI was helpful in evaluating children with atypical idiopathic scoliosis or congenital scoliosis, gait abnormality, limb pain or weakness, or rigid or recurrent foot deformities. Given the high frequency of occult spinal cord abnormality in children with severe foot deformity, the use of screening spine MRI may be especially useful in this group.     

Comparative analysis of non-adherence to medication treatment for systemic arterial hypertension in urban and rural populations

OBJECTIVE:

to evaluate the indexes and the main factors associated with non-adherence to medication treatment for systemic arterial hypertension between urban and rural areas.

METHOD:

analytical study based on an epidemiological survey with a sample of 247 hypertensive residents of rural and urban areas, with application of a socio-demographic and economic questionnaire, and treatment adherence assessment. The Pearson''s Chi-square test was used and the odds ratio (OD) was calculated to analyze the factors related to non-adherence.

RESULTS:

the prevalence of non-adherence was 61.9% and it was higher in urban areas (63.4%). Factors significantly associated with non-adherence were: male gender (OR=1.95; 95% CI 1.08-3.50), age 20-59 years old (OR=2.51; 95% CI 1.44-4.39), low economic status (OR=1.95; 95% CI 1.09-3.47), alcohol consumption (OR=5.92, 95% CI 1.73-20.21), short time of hypertension diagnosis (OR=3.07; 95% CI 1.35-6.96) and not attending the health service for routine consultations (OR=2.45; 1.35-4.42).

CONCLUSION:

the socio-demographic/economic characteristics, lifestyle habits and how to relate to health services were the factors that presented association with non-adherence regardless of the place of residence.     

Differential Effects of Anesthetics on Mitochondrial KATP Channel Activity and Cardiomyocyte Protection

Background: Mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels play a pivotal role in mediating cardiac preconditioning. The effects of intravenous anesthetics on this protective channel have not been investigated so far, but would be of importance with respect to experimental as well as clinical medicine.

Methods: Live cell microscopy was used to visualize and measure autofluorescence of flavoproteins, a direct reporter of mitoKATP channel activity, in response to the direct and highly selective mitoKATP channel opener diazoxide, or to diazoxide following exposure to various anesthetics commonly used in experimental and clinical medicine. A cellular model of ischemia with subsequent hypoosmolar trypan blue staining served to substantiate the effects of the anesthetics on mitoKATP channels with respect to myocyte viability.

Results: Diazoxide-induced mitoKATP channel opening was significantly inhibited by the anesthetics R-ketamine, and the barbiturates thiopental and pentobarbital. Conversely, urethane, 2,2,2-trichloroethanol (main metabolite of [alpha]-chloralose and chloral hydrate), and the opioid fentanyl potentiated the channel-opening effect of diazoxide, which was abrogated by coadministration of chelerythrine, a specific protein kinase C inhibitor. S-ketamine, propofol, xylazine, midazolam, and etomidate did not affect mitoKATP channel activity. The significance of these modulatory effects of the anesthetics on mitoKATP channel activity was substantiated in a cellular model of simulated ischemia, where diazoxide-induced cell protection was mitigated by R-ketamine and the barbiturates, while urethane, 2,2,2-trichloroethanol, and fentanyl potentiated myocyte protection.