Phytochemical characterization and antidiabetic analysis of Bauhinia holophylla extract on the maternal-fetal outcomes of rats.

This study aims to evaluate the phytochemical properties of Bauhinia holophylla (Bong.) Steud leaf extract, and their impact on maternal reproductive and fetal development in diabetic rats. For this, adult female Wistar rats (100 days of life) received streptozotocin (40 mg/Kg, intraperitoneal) for induction of diabetes, were mated and distributed into four groups: Nondiabetic; Nondiabetic given B. holophylla; Diabetic; and Diabetic given B. holophylla. The plant extract was given by gavage at increasing doses: 200, 400, and 800 mg/Kg. At day 21 of pregnancy, liver and blood samples were obtained for oxidative parameters and biochemical analysis, respectively. The uterus was removed for maternal-fetal outcomes. Phytochemical analysis showed a high content of phenolic components and biogenic amines. B. holophylla extract did not alter the glycemic levels but improved the lipid profile in diabetic animals. Besides that, the number of live fetuses and maternal weight gain were decreased in Diabetic group, and were not observed in animals treated. The group Diabetic treated presented a higher percentage of fetuses classified as adequate for gestational age compared to the Diabetic group. However, the treatment with plant extract caused embryo losses, fetal growth restriction, and teratogenicity in nondiabetic rats. Thus, the indiscriminate consumption requires carefulness.

Analysis of Risk Factors for a Low Immune Response to Messenger RNA COVID-19 Vaccine in Kidney Transplant Recipients and Differences Between Second and Third Dose.

BACKGROUND: The efficacy of the response to SARS-CoV-2 vaccination in kidney transplant recipients is low. The aim of our study was to evaluate the risk factors correlated with the low antibody response and whether there was an improvement between the second and the third dose. METHODS: A prospective study was conducted on 176 kidney transplant recipients who received the second and the third dose of the anti-SARS-CoV-2 mRNA Comirnaty vaccine. We evaluated the seroconversion process after administration of the second and the third dose and assessed a possible correlation with age, time between transplant and vaccination, and type of immunosuppressive therapy. RESULTS: A total of 98 of the 176 patients (55.7%) responded positively after the inoculation of the second dose and according to the multivariable logistic regression analysis the lack of seroconversion was independently associated with patient age ≥60 (P = .025; odds ratio [OR], 2.094), time since transplant of 1 to 3 months (P = .032; OR, 2.118), and triple therapy (P = .044; OR, 2.327). After the vaccine third dose, the seroconversion increased to 62.5%, and it was negatively influenced by calcineurin inhibitor use (12/21, 57.1% vs 71/78, 91.0%, P = .0006) and triple therapy (13/21, 61.9% vs 72/78, 92.3%, P = .0014). The median of antispike antibody response significantly increased from 18.5 IU/mL after the second dose to 316.9 IU after the third dose (P < .0001). CONCLUSIONS: We demonstrated a correlation between older age and shorter distance from the transplant and triple immunosuppressive therapy with the lack of seroconversion. We noticed a significant improvement in antibody response by a third dose of messenger RNA vaccine.

Phosphorylation of human estrogen receptor alpha by protein kinase A regulates dimerization.

Phosphorylation provides an important mechanism by which transcription factor activity is regulated. Estrogen receptor alpha (ERalpha) is phosphorylated on multiple sites, and stimulation of a number of growth factor receptors and/or protein kinases leads to ligand-independent and/or synergistic increase in transcriptional activation by ERalpha in the presence of estrogen. Here we show that ERalpha is phosphorylated by protein kinase A (PKA) on serine-236 within the DNA binding domain. Mutation of serine-236 to glutamic acid prevents DNA binding by inhibiting dimerization by ERalpha, whereas mutation to alanine has little effect on DNA binding or dimerization. Furthermore, PKA overexpression or activation of endogenous PKA inhibits dimerization in the absence of ligand. This inhibition is overcome by the addition of 17beta-estradiol or the partial agonist 4-hydroxy tamoxifen. Interestingly, treatment with the complete antagonist ICI 182,780 does not overcome the inhibitory effect of PKA activation. Our results indicate that in the absence of ligand ERalpha forms dimers through interaction between DNA binding domains and that dimerization mediated by the ligand binding domain only occurs upon ligand binding but that the complete antagonist ICI 182,780 prevents dimerization through the ligand-binding domain. Heterodimer formation between ERalpha and ERbeta is similarly affected by PKA phosphorylation of serine 236 of ERalpha. However, 4-hydroxytamoxifen is unable to overcome inhibition of dimerization by PKA. Thus, phosphorylation of ERalpha in the DNA binding domain provides a mechanism by which dimerization and thereby DNA binding by the estrogen receptor is regulated.

Analysis of changes in optical fibers during arc-fusion splicing by use of quantitative phase imaging.

A non-interferometric imaging technique in conjunction with Abel inversion is used to directly and quantitatively examine the changes in optical fibers due to the heating produced during arc-fusion splicing as a function of fusion arc parameters. Phase images in the vicinity of a fusion splice are obtained using Quantitative Phase Microscopy, allowing the refractive-index change to be reconstructed with high spatial resolution. This simple, nondestructive method confirms that, for a fixed arc current, while the fusion time increases, the refractive-index of both fiber cores within the fusion region decreases in magnitude, the core region broadens, and the axial gradient decreases.

Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo.

PURPOSE: Trichostatin A (TSA), an antifungal antibiotic with cytostatic and differentiating properties in mammalian cell culture, is a potent and specific inhibitor of histone deacetylase (HDAC) activity. The purpose of this study was to evaluate the antiproliferative and HDAC inhibitory activity of TSA in vitro in human breast cancer cell lines and to assess its antitumor efficacy and toxicity in vivo in a carcinogen-induced rat mammary cancer model. EXPERIMENTAL DESIGN AND RESULTS: TSA inhibited proliferation of eight breast carcinoma cell lines with mean +/- SD IC(50) of 124.4 +/- 120.4 nM (range, 26.4-308.1 nM). HDAC inhibitory activity of TSA was similar in all cell lines with mean +/- SD IC(50) of 2.4 +/- 0.5 nM (range, 1.5-2.9 nM), and TSA treatment resulted in pronounced histone H4 hyperacetylation. In randomized controlled efficacy studies using the N-methyl-N-nitrosourea carcinogen-induced rat mammary carcinoma model, TSA had pronounced antitumor activity in vivo when administered to 16 animals at a dose of 500 microg/kg by s.c. injection daily for 4 weeks compared with 14 control animals. Furthermore, TSA did not cause any measurable toxicity in doses of up to 5 mg/kg by s.c. injection. Forty-one tumors from 26 animals were examined by histology. Six tumors from 3 rats treated with TSA and 14 tumors from 9 control animals were adenocarcinomas. In contrast, 19 tumors from 12 TSA-treated rats had a benign phenotype, either fibroadenoma or tubular adenoma, suggesting that the antitumor activity of TSA may be attributable to induction of differentiation. Two control rats each had tumors with benign histology. CONCLUSIONS: The present studies confirm the potent dose-dependent antitumor activity of TSA against breast cancer in vitro and in vivo, strongly supporting HDAC as a molecular target for anticancer therapy in breast cancer.

Depression and neuropsychological performance in asymptomatic HIV infection.

OBJECTIVE: The authors examined the effect of depression on neuropsychological performance in HIV-infected men. Previous studies have suggested that depression may account for the neuropsychological abnormalities observed in some patients with HIV infection, but few studies have specifically examined this question. METHOD: An extensive neuropsychological test battery was administered to 121 HIV-seropositive asymptomatic men and 42 HIV-seronegative comparison subjects. The seropositive subjects were grouped into depressed and non-depressed groups on the basis of scores on the Beck Depression Inventory, Hamilton Rating Scale for Depression, and Structured Clinical Interview for DSM-III-R. RESULTS: Statistical comparisons revealed very few measures on which the depressed seropositive subjects scored significantly worse than either of the nondepressed comparison groups. The nondepressed seropositive group differed consistently from the seronegative comparison subjects on measures of verbal memory and dexterity. CONCLUSIONS: These data indicate that the subtle neuropsychological abnormalities observed in some asymptomatic HIV-seropositive subjects cannot be attributed to depression. These data also indicate the advantages of a multifaceted approach to assessment of depression.

Correction of a lysosomal deficiency by contact-mediated enzyme transfer after bone marrow transplantation.

The effectiveness of bone marrow transplantation for treating lysosomal deficiency diseases relies on the ability of bone marrow cells to provide the missing enzyme to various tissues of the recipient. This has been shown to occur in vitro by endocytosis of enzyme secreted by bone marrow-derived cells and also by direct cell-to-cell-contact. To investigate the mechanism of enzyme replacement therapy in vivo we have used, as enzyme donors, bone marrow cells from coat color mouse mutants that secrete very low or very high levels of a lysosomal enzyme, beta-glucuronidase. Our results show that the level of beta-glucuronidase activity acquired by the tissues of recipient, enzyme-deficient mice is not related to the ability of the donor bone marrow-derived cells to secrete the missing enzyme. This finding suggests that cell-to-cell transfer of lysosomal enzymes may play an important role in the correction of lysosomal diseases by bone marrow transplantation.

Refractive index profiles of Ge-doped optical fibers with nanometer spatial resolution using atomic force microscopy.

We show a quantitative connection between Refractive Index Profiles (RIP) and measurements made by an Atomic Force Microscope (AFM). Germanium doped fibers were chemically etched in hydrofluoric acid solution (HF) and the wet etching characteristics of germanium were studied using an AFM. The AFM profiles were compared to both a concentration profile of the preform determined using a Scanning Electron Microscope (SEM) and a RIP of the fiber measured using a commercial profiling instrument, and were found to be in excellent agreement. It is now possible to calculate the RIP of a germanium doped fiber directly from an AFM profile.

Repeated methacholine challenge produces tolerance in normal but not in asthmatic subjects.

Repeated methacholine challenge in normal nonasthmatic subjects (who require higher doses of methacholine than do asthmatic subjects to produce a 20 percent decrease in FEV1) can produce progressively diminishing methacholine responsiveness (or tolerance) with serial challenges. To determine whether tolerance to methacholine occurs in asthmatic subjects as it does in nonasthmatic subjects, we studied eight young (mean age, 24 years) mild asthmatic patients (occasional but not regular use of bronchodilator medications, PC20 methacholine range 0.1 to 7.0 mg/ml) who underwent five sequential methacholine challenges at 1.5-h intervals. Serially increasing concentrations of methacholine were given until FEV1 fell by 20 percent. Results were compared with those in seven nonasthmatic control subjects who underwent an identical protocol. As seen in previous studies, the normal subjects demonstrated significant tolerance to methacholine when each of five challenges was compared to the first. By contrast, in the asthmatic group, the mean cumulative dose of methacholine producing a 20 percent fall in FEV1 in the fifth challenge was not significantly different from the dose required in the first challenge. These results indicate that marked tolerance to methacholine does not occur in mild asthmatic patients with multiple repeated challenges over 6 h. The lower cumulative dose of methacholine required by asthmatic patients may be insufficient to produce tolerance.

Ethics of obesity treatment: implications for dietitians.

Dietitians face both a responsibility and an opportunity to address the ethical issues of obesity treatment and to promote weight management strategies that are beneficial and effective. The Code of Ethics for the Profession of Dietetics, which was adopted in 1989 to provide guidance to dietetics practitioners in their professional practice and conduct, can serve as a guide in an evaluation of current obesity treatments. Dietitians must help clients be realistic about their weight loss goals and address emotional conflicts that may be undermining weight management efforts. Referrals to therapists may be indicated, and dietitians must be prepared to recognize the need and make the recommendations. Dietitians should take the lead in developing more ethical and beneficial treatments by collaborating with government and industry to protect the consumer from ineffective or potentially harmful practices.

Intervention specialist: new role for dietitians' counseling skills.

Dietitians who want to expand their clinical responsibilities beyond dietary counseling should consider the role of the intervention specialist. The role is a logical expansion of the duties of the dietitian who is already serving as a health behavior counselor. The concept of dietitians' functioning as intervention specialists originated in clinical trials, when they served as adherence counselors. The intervention specialists in the clinical trials used the health behavior counseling process to help research participants adhere to the trials' protocols. This counseling process uses a systematic, problem-solving approach to assess, diagnose, intervene, and follow up on a targeted behavioral problem. Dietitians can prepare for the expanded counseling role of intervention specialist through interviewing and counseling skill assessment and further training. They must take an active role in defining how the services of an intervention specialist can be beneficial to physicians as well as to their patients. They should address the cost-effectiveness of behavior counseling in order to justify the increased initial costs. Dietitians will need to actively promote the role of intervention specialist in the medical community if they want this opportunity for increased professional responsibility.

Airway reactivity in welders: a controlled prospective cohort study.

In a 3-year survey, respiratory symptoms, spirometry, and methacholine reactivity were measured annually in welders (n = 51) and non-welder controls subjects (n = 54) to determine whether welding-related symptoms are associated with accelerated decline in lung function or changes in airway reactivity. In the cross-workshift study, maximal midexpiratory flow rate declined reversibly during a welding day, whereas 1-second forced expiratory volume and forced-vital capacity were unchanged. In the longitudinal study, the welders had significantly more reversible work-related symptoms of cough, phlegm, wheeze, and chest tightness than the non-welder shipyard control subjects. In this group of actively working welders, across-workshift changes in midflow and reversible symptoms were related to the welding occupation, but evidence for chronic irreversible effects on spirometry or airway reactivity was not seen over the 3 years of observation. The short period of observation was not optimal for detecting a chronic effect on lung function. Work practices and engineering controls may be successfully preventing irreversible respiratory effects, but not mild reversible effects, in this group of welders.

Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo.

Gliotoxin is a natural mycotoxin with immunosuppressive and antimicrobial activity. Inhibition of farnesyltransferase (IC50 80 microM) and geranylgeranyltransferase I (IC50 17 microM) stimulated interest in the potential antitumor activity of this epidithiodioxopiperazine. Gliotoxin inhibited proliferation of six breast cancer cell lines in culture with mean +/- SD IC50 289 +/- 328 microM (range 38-985 microM); intracellular farnesylation of Lamin B and geranylgeranylation of Rap1A were inhibited in a dose-dependent manner. In randomized controlled studies using the N-methyl-N-nitrosourea rat mammary carcinoma model, gliotoxin had pronounced antitumor activity in vitro and little systemic toxicity when administered to 10 animals at 10 mg/kg by subcutaneous injection weekly for 4 wk compared with 10 controls. Single doses up to 25 mg/kg were well tolerated. The present studies confirm that gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with pronounced antitumor activity and favorable toxicity profile against breast cancer in vitro and in vivo.

Proposal of new gradual dilation metal dilators.

The Authors suggest a new conceived line of metal cervical dilators, testing them on a group, made up of 69 patients, who will undergo Voluntary Pregnancy Interruption (VPI). Comparing the results with those obtained within a further test-group, made up of 69 women who have undergone a cervical dilation, performed by traditional Hegar dilators, it has been noticed that the new dilators are less traumatic on the cervical canal of the uterus; they can be used more easily and a wider employment is foreseen.

PIP: A set of 5 newly cervical dilators was tested on a group of 69 patients having abortion before the 3rd month of gestation, in comparison with 69 on which Hegar dilators were used. The new dilators are cone shaped, 190 mm in length, with a working length of 50 mm corresponding to the length of uterus from the os to the fundus. The minimum and maximum diameters were calculated as a function of the vertex angle, with each instrument's diameter larger than the preceding one. Calculations of design parameters, drawings and photographs are shown. cervical dilation of the subjects was assessed with Hegar dilators before the procedure began and at follow up 1 month later. Among both multiparas, and nulliparas and women with only cesarean deliveries, the cervical dilation as follow up was increased in a higher proportion of the group that had been dilated with Hegar dilators than in those dilated with the new dilators. There were no complications or fevers in these subjects. These new dilators caused less trauma as shown by cervical dilation at follow up, allowed less operative and anesthesia time, and fewer instruments, 5 instead of 20 Hegar dilators.

[20 years (1960-1980) of bacterial meningitis in childhood. II. Therapy and diagnosis]. / 20 anni (1960-1980) di meningite batterica nell'infanzia. II. Terapia e diagnosi.

In this article we review the global therapy for purulent meningitis in childhood and present personal data derived from a twenty year survey study (1960 to 1980). We recommend the prompt use of adequate antibiotics at correct doses largely following the intravenous pathway in order to achieve active antimicrobial levels in the cerebrospinal fluid. On the basis of our experience we favour a more large use of either systemic chloramphenicol or intrathecal even in the neonatal period. Moreover, we think glucose infusions should be employed with great caution due to worsening of metabolism (lactate accumulation) and perfusion in the cerebral tissue.

[20 years (1960-1980) of bacterial meningitis in childhood. I. Epidemiological and clinical data]. / 20 anni (1960-1980) di meningite batterica nell'infanzia. I. Dati epidemiologici e clinici.

One hundred forty six children having suffered bacterial meningitis at any age have been collected and retrospectively studied over a period of a twenty year survey (1960 to 1980). In our series we can confirm the prominent epidemiologic and clinical features emerging from the literature. It is notewborty to outline the great percentage of cases lacking any bacterial identification due to previous antimicrobial treatment for parameningeal foci. This raises some major problems about early diagnosis, validity and signification of lumbar punctures, and usefulness of starting treatment with large spectrum antibiotics.

[Congenital hydrocephalus: clinico-pathological picture]. / L'idrocefalia congenita: quadri clinico-patologici.

The authors review the main pathologic causes of congenital hydrocephalus from ischemic-vascular injuries, embryofoetal infections and dysraphisms to genetic ones. Abundant illustrations of each condition are furnished and particular attention is paid to each situation, discussing the available pathogenetic mechanisms and hypothesis. Genetic "sine causa" hydrocephalus and X-linked hydrocephalus are mainly stressed, presenting some personal data. The clinic aspects of the varying forms of hydrocephalus are continuously kept in mind and a terminal paragraph details the clinical and neuroradiological means determinant in differential diagnosis versus similar conditions such as hydranencephaly, porencephaly, aracnoid cysts, holoprosencephaly and agenesis of corpus callosum.

[Neuropathology of the Turner syndrome]. / Neuropatologia della sindrome di Turner.

We report the neuropathologic examination of a neonatal case of Turner's syndrome (45,XO). We have found some mild irregularities in the cortical organization, notably in frontal and hippocampal regions. In the frontal cortex such anomalies affected particularly the more superficial layers essentially sparing the migrating process which was largely achieved in its fundamental phases. The hippocampal dentate gyrus appeared abnormally infolded. The cerebellum was hypoplasic and contained three types of abnormalities, at least: abundant paradentate matrix cell nests, a large mass of dysplastic cerebellar gyri along the ventral wall of the 4th ventricle and, finally, multiple voluminous heterotopias of macroneurons (possibly, Purkinje cells) in the subcortical white matter. In addition, there were two small olivary heterotopias in the medulla oblongata. The correct identification of all neuropathologic anomalies has been possible for having employed the method of whole brain serial sectioning. We have correlated such cortical, cerebellar and truncal abnormalities to those encountered in similar conditions as lissencephaly, Zellweger's disease and chromosomal trisomies. The pathogenetic mechanisms triggered by the absence of an X chromosome can affect the neuronal migration, but only after the cortical hemispheric one has been almost completely ended. This could explain why cerebellar and olivary neuronal migration are exclusively affected, being there the migration process chronologically slowed down during the normal neurogenesis. There means we might date after the 4th fetal months the neuronal migration trouble. Finally, we would suggest the soft cortical changes in such crucial regions as the frontal and hippocampal cortex to be possibly responsible for the degree of mental retardation seen in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Gender, lifestyles, illness perception and stress in stable atrial fibrillation.

AIMS: The study is aimed at investigating if perceived stress in Stable Atrial Fibrillation (AF) has any gender-associated feature and relationships with lifestyle indicators and education level, and which relationship self efficacy, anxiety and depression and illness perception have, if any. PATIENTS AND METHODS: 88 consecutive patients referred for stable AF are studied by Psychological Stress Measure (PSM) test, Illness Perception Questionnaire (IPQ-R), Generalized Self-Efficacy scale (GSE) and Hospital Anxiety and Depression Scale (HADS). Mediterranean diet, physical activity increase and smoking withdrawal counseling were provided. RESULTS: AF patients have higher PSM associated with gender (women), older age, anxiety and depression. Higher GSE, greater Adherence to Mediterranean Diet profile and coffee habits (greater coffee users) are associated with a reduced hazard of perceived stress. By multiple linear regression, PSM is explained by Anxiety and IPQr (statistically significant are emotional representation and illness coherence subscales), which account for 92.2% of the variance (p<0.0001). CONCLUSION: Our results outline that psychological stress is greater in women in comparison with men. Illness perceptions are important in the context of perceived stress in AF. This effect appears to be modulated by greater self-efficacy and by Adherence to Mediterranean Diet profile, that when higher, are associated with a reduced hazard of perceived stress. We suggest that therapeutic interventions on illness perceptions can be warranted in order to achieve a lower psychological distress in AF patients.

Stress, abdominal obesity and intrarenal resistive index in essential hypertension.

AIM: Although it is commonly believed that a strong causal link exists between psychological stress and hypertension, as well with other factors, such as obesity, just what kind of empirical evidence supports this assumption is still controversial. The aim of the study is to investigate if perceived stress have any interference with intrarenal resistance and hence with mechanisms related to Essential Hypertension (EH) and if Anxiety, Depression, Self efficacy and Illness Perception can account for perceived stress. PATIENTS AND METHODS: Obesity, insulin resistance (HOMA), Doppler Renal Resistive Index (RRI) and glomerular filtration rate (GFR) are studied along with Psychological Stress Measure (PSM), Illness Perception Questionnaire (IPQ-R), Generalized Self-Efficacy scale (GSE) and Hospital Anxiety and Depression Scale (HADS) in 119 hypertensive patients referred for stable lasting EH, and 150 normal controls. Lower salt/lower calories Mediterranean diet, physical activity increase and smoking withdrawal counseling were provided. RESULTS: By Odds Ratios, higher risk of EH is associated with greater perceived stress, older age, lower GFR, obesity, greater RRI and insulin resistance. By Multiple Linear Regression the most significant variable that accounts for higher RRI are abdominal obesity and arterial pulse pressure; the only significant independent psychological variable that accounts for abdominal obesity are PSM and identity IPQ subscale. Self-Efficacy anxiety and Illness perception subscales (IPQr), accounts significantly for 62.0% of the variance to PSM, with possible effects on RRI and on the pathophysiological hypertension cascade. CONCLUSION: Worst identity and treatment control perceptions of EH, and a lower self-efficacy are the main psychological factors accounting for a greater stress. Interventions aimed to reduce perceived stress can be warranted in EH.