The promoter region (-800, -509) polymorphisms of transforming growth factor-beta1 (TGF-beta1) gene and recurrent spontaneous abortion

Recurrent spontaneous abortion (RSA) is regarded as a common pregnancy complication in southern Iran. The exact causes of RSA are not yet known. Transforming growth factor-beta1 (TGF-beta1) is produced by T regulatory lymphocytes (Treg), which play an important role in the physiology of pregnancy. Several polymorphisms of the TGF-beta1 gene have been reported, some with important correlation with disease severity. In this investigation, the polymorphism of the TGF-beta1 gene at promoter region positions -800 (G/A) and -509 (C/T) was studied in 111 RSA and 110 normal female subjects from southern Iran by PCR-RFLP. Results indicated that at position -800 (G/A) polymorphism, 75.7% of RSA cases and 77.3% of normals were homozygote GG. In addition, 23.4% of cases and 22.7% of normal individuals were heterozygote AG. Only one of the patients appeared to be homozygote AA. None of the normal individuals were found to be homozygote AA at this position. In the case of the -509 (C/T) polymorphism, 38.7% of patients and 28.2% of controls were homozygote CC. While 40.6% of cases and 50.9% of normal individuals were heterozygote CT, 20.7% of RSA cases and 20.9% of controls were homozygote TT. The results indicate that there are no statistically significant differences of genotype distribution and allele frequency between RSA cases and controls at both polymorphic sites. In conclusion, the promoter region polymorphisms of TGF-beta1 at positions -800 (G/A) and -509 (C/T) may not be associated with RSA.     

Pro-oxidant activity of zuclopenthixol in vivo: differential effect of the drug on brain oxidative status of scopolamine-treated rats

Several clinical studies implicated oxidative stress in the pathophysiology of both psychosis and dementia. As dementia is commonly associated with psychosis, antipsychotic medications are of importance in the pharmacotherapy of dementia particularly as a number of antipsychotics were reported to demonstrate neuronal pro-oxidant and/or antioxidant properties. Impairment of learning and memory, as the most characteristic manifestation of dementia, could be induced in experimental animals by acute administration of scopolamine (SCO) with a resultant elevation in brain oxidative status. This study investigated the potential pro-oxidant and/or antioxidant activity of the antipsychotic drug zuclopenthixol acetate, as its effect on brain oxidative status has yet to be evaluated. A 2 x 3 between-subjects factorial design was used to investigate the simultaneous and interactive effects of zuclopenthixol (0.7 and 1.4 mg/kg i.p.) and SCO on rat brain malondialdehyde, glutathione, glutathione peroxidase and superoxide dismutase levels/activities. Results revealed a significant pro-oxidant effect for both zuclopenthixol and SCO alone conditions. In addition, combined treatment of zuclopenthixol and SCO was found to be significantly different compared to either treatment conditions with regard to their effect on different brain oxidative stress indices. Such findings may have valuable implications in the pharmacotherapy of both psychosis and dementia.     

In vitro osteoclast resorption of bone substitute biomaterials used for implant site augmentation: a pilot study

PURPOSE: This observational study examined the resorptive behavior of normal neonatal rabbit osteoclasts grown on slices of bovine cortical bone as compared to samples of commercially available bone substitute biomaterials. It also examined the surface characteristics of these materials. MATERIALS AND METHODS: The 11 materials tested fell into 3 groups: (1) bone-derived, including freeze-dried human rib block, human demineralized freeze-dried bone, and deproteinated bovine bone; (2) synthetic hydroxyapatites (HA); and (3) synthetic non-HA, including coated methacrylates and coated silica glass. After 4 days in culture, 1 group of samples of each material underwent scanning electron microscopy (SEM) to evaluate resorptive pitting versus controls, while another group underwent tartrate-resistant acid phosphatase staining and light microscopy to examine osteoclast numbers and morphology. The 2 bovine-derived HA materials also underwent immunohistochemical staining and surface chemistry analysis. RESULTS: While most of these materials supported osteoclast attachment, some spreading, and survival in culture, only the bone-derived materials, with the exception of sintered deproteinated bovine bone, showed large scalloped-edged resorption pits with trails and exposed collagen when examined by SEM, although not to the same extent as unprocessed natural bone material. The HA materials and the sintered deproteinated bovine bone showed evidence of etching with smaller pits but no evidence of resorptive trail formation. The non-HA materials showed no evidence of pit formation or trails. Under immunohistochemical staining, Bio-Oss appeared to be positive for type I collagen after osteoclast activity on its surface, while Osteograf/N showed no positive staining. Surface chemistry analysis revealed nitrogen present in Bio-Oss specimens (0.17% to 0.47%), while there was no nitrogen detected in the Osteograf/N (0.00%); the percent nitrogen observed in normal bovine bone controls was 6.01% to 9.25%. DISCUSSION: The bone-derived materials supported osteoclast activity on the material surface in a way that facilitated formation of the more complex resorption pits in vitro. Assuming the rate of pit formation observed in vitro mimics that observed in vivo, the quantity and type of osteoclastic remodeling seen on non-bone-derived materials--and perhaps sintered bone-derived materials--would be extremely slow to negligible. Physiologic removal of non-bone-derived bone substitutes in vivo may occur by methods other than osteoclast resorption. CONCLUSIONS: Allogenous and xenogenous bone-derived materials that undergo delayed physiologic resorption may be more appropriately used with a staged surgical approach when used in sites intended to support osseointegrated dental implants. The combination of collagen staining and the presence of nitrogen suggest that there may be residual protein in Bio-Oss.     

Characteristics of long-term live-donor renal allograft survivors

BACKGROUND/AIMS: Despite the high rate of rejection, allograft failure and patient mortality in the early years of renal allotransplantation, some patients have done-remarkably well. We report here on 62 renal transplant recipients out of 144 patients (43%) who had functioning grafts for more than 15 years (range 15-24 years). MATERIALS: Demographic and follow-up data for patients fulfilling the criteria were reviewed. These patients include 43 males and 19 females, with a mean age at transplantation of 27.5 +/- 6.6 years (range 9-43 years), and mean donor age of 30 +/- 8.6 years. The donor source was 8 parents, 49 siblings and 5 unrelated. The main causes of end-stage renal disease were chronic pyelonephritis and chronic glomerulonephritis. Twenty-nine patients were treated with cyclosporine (CsA) while 33 patients were primarily immunosuppressed by steroids and azathioprine. RESULTS: Acute rejection episodes occurred in 40 patients (64.3%), out of them 19 patients experienced two or more acute rejection episodes. Univariate analysis showed that recipient and donor age, HLA-DR matching, pre- and post-transplant hypertension, ATN, delayed diuresis and chronic allograft nephropathy are significant risk factors; while recipient age, delayed diuresis and post-transplant hypertension were still significant by multivariate analysis. CONCLUSIONS: We concluded that renal transplantation, even in its earliest years and despite the numerous complications, has provided 15 or more years of near-normal life to patients with end-stage renal disease. Certain characteristics of long-term renal allograft survivors include young donor/recipient pairs, good DR matching with less pre- and post-transplantation prevalence of hypertension.     

Breast Cancer Knowledge and Related Behaviors among Women in Abha City, Southwestern Saudi Arabia

Breast cancer is the most common malignancy among women in Saudi Arabia. A cross-sectional study was conducted on 1,092 women attending urban primary health care centers in Abha City southwestern Saudi Arabia about breast cancer knowledge, attitudes, and related practices. Only 22.0 % heard about mammography, and 41.5 % heard about breast self-examination (BSE). More than half of the women in the study identified changes occurring in case of breast cancer and identified risk factors. Only 8.3 % were examined by clinical breast examination (CBE), 6.2 % were examined by mammography, and 29.7 % performed BSE. The study points to the insufficient knowledge of women and the low practice of BSE, CBE, and mammography. Public awareness should be enhanced by all available means including mass media, schools, social gatherings, and waiting areas in primary health care centers. There is an urgent need for continuing medical education programs for health care workers in the region concerning breast cancer.     

The Role of Genetic Variants (rs869109213 and rs2070744) Of the eNOS Gene and BglII in the α2 Subunit of the α2β1 Integrin Gene in Diabetic Retinopathy in a Tunisian Population

Purpose: In this study, we investigated the association of two polymorphisms (rs869109213 and rs2070744) in the eNOS gene and one polymorphism BglII in the α₂β₁ integrin gene (ITGA2) with the risk of diabetic retinopathy (DR) in a Tunisian population.

Methods: The study investigated of 110 type 2 diabetes mellitus (T2DM) and 127 DR patients. The genotypes of the eNOS 4b/4a (rs869109213) and ?786T/C (rs2070744) polymorphisms and of the BglII polymorphism of ITGA2 were studied using the PCR or PCR-RFLP method.

Results: The genotype distributions of the two polymorphisms in eNOS 4b4a and eNOS (?786T/C) were significantly different between T2DM and DR patients (p < .004 and p = .033, respectively). These polymorphisms were associated with the risk of DR (OR = 2.65, 95%CI [1.45–4.84], p = .002) for the eNOS 4b4a genotype and (OR = 2.43, 95%CI [1.06 ? 5.56], p = .036) for the CC genotype of the eNOS gene (?786T/C). Similarly, the genotype distribution of the BglII polymorphism was significantly different between the two groups studied (p = .037). This polymorphism was associated with an increased risk of DR (OR = 4.03, 95% CI [1.17 ? 7.85], p = .022) for BglII(+/+).

Conclusion: The present study suggests that the polymorphisms 4b4a and ?786T/C in the eNOS gene might be associated with DR. In addition, the BglII polymorphism in the ITGA2 gene was a risk factor for DR.     

Modeling the Parameters Involved in Preparation of PLA Nanoparticles Carrying Hydrophobic Drug Molecules Using Artificial Neural Networks

Purpose

Artificial neural networks (ANNs) are used to optimize a formulation of poly(lactic acid) (PLA) nanoparticles containing hydrophobic drug molecules through a study of the critical parameters affecting nanoparticle size.

Methods

We evaluate the effect of input variables, including concentrations of PLA and Tween 80, amplitude of ultrasound wave, and sonication time on the formation of PLA nanoparticles, which were prepared using a solvent evaporation method. Budesonide was used as a model hydrophobic drug. An ANN model was created using training data and evaluated for prediction capability using validation data.

Results

The ANN model demonstrated that reducing PLA concentration and increasing Tween 80 concentration provided optimum conditions for the preparation of small particle size. Additionally, the simultaneous use of high sonication time and amplitude has an adverse effect on particle diameter.

Conclusion

By defining the effects of each parameter on the size of PLA nanoparticles, this study demonstrated the feasibility of using an ANN model to optimize the conditions for achieving minimum particle size in hydrophobic drug-loaded PLA nanoparticles.     

Beyond “patient-provider race matching.” Black midwives clarify a vision for race-concordant care to achieve equity in Black perinatal health: A commentary on “Do Black birthing persons prefer a Black health care provider during birth? Race concordance in birth”

Racial concordance has been identified as a potential strategy to improve the perinatal health of Black women and birthing people by mitigating implicit bias and improving mutual trust, healthy communication, and satisfaction. In a recent article published in BIRTH: Issues in Perinatal Care, Bogdan-Lovis et al. surveyed 200 Black women to determine whether they possessed a race and gender practitioner preference for their birth practitioner and examined whether race and gender concordance was associated with greater birth satisfaction and perceived respect, trust, practitioner competence, empathy, and use of inclusive communication. In this commentary, written by a group of Black midwives, we respond to the study and offer a vision for race-concordant care that encompasses cultural safety provided in a community-based setting.     

Protective effects of curcumin against ischaemia/reperfusion insult in rat forebrain.

Oxidative stress is believed to be implicated in the pathogenesis of postischaemic cerebral injury. Many antioxidants were shown to be neuroprotective in experimental models of cerebral ischaemia/reperfusion (I/R). The present study was designed to investigate the potential protective effects of curcumin (CUR) against I/R insult in rat forebrain. The model adopted was that of surgically-induced forebrain ischaemia, performed by means of bilateral common carotid artery occlusion (BCCAO) for 1 h, followed by reperfusion for another 1h. The effects of a single i.p. dose of CUR (50, 100 or 200 mg kg(-1)), administered 0.5 h after the onset of ischaemia, were investigated by assessing oxidative stress-related biochemical parameters in rat forebrain. CUR, at the highest dose level (200 mg kg(-1)), decreased the I/R-induced elevated xanthine oxidase (XO) activity, superoxide anion (O(2)*(-)) production, malondialdehyde (MDA) level and glutathione peroxidase (GPx), superoxide dismutase (SOD), and lactate dehydrogenase (LDH) activities. On the other hand, CUR did not affect the declined reduced glutathione (GSH) content due to I/R insult. Worth mentioning is that the activity of catalase (CAT) did not change in response to either I/R insult or drug treatment. In conclusion, CUR was found to protect rat forebrain against I/R insult. These protective effects may be attributed to its antioxidant properties and/or its inhibitory effects on xanthine dehydrogenase/xanthine oxidase (XD/XO) conversion and resultant O(2)*(-) production.