Prevention is better than cure: identifying and dealing with the key features involved in the prevention of gestational diabetes - A bird's eye view.

Gestational diabetes (GDM) is considered to be the most common metabolic problem of pregnancy, which, if not recognized and treated on time, can lead to devastating effects on both the mother's health and the health of the fetus and the newborns. Many studies have revealed that the children born of GDM mothers or grandmothers have higher chances of developing diabetes type I or type II later in their life. Early identification of risk factors can help prevent the appearance of severe GDM and its complications witnessed both in the child and the mother. Obesity is one of the major risk factors that should not be ignored, and obese females should first undergo weight reduction plans in case of planned pregnancies. Other risk factors include a family history of DM arterial hypertension, significant weight gain during pregnancy, short sleep duration, women's exposure to stressful environments, changes in alpha and beta microbiota, and air pollution. Proper care should be provided to females of reproductive age both before and during pregnancy to avoid complications. Awareness programs for healthy lifestyles and diets, oral hygiene maintenance guides, and regular health check-ups can all be considered as a key to a healthy society. Expanding the analysis of gut microbiota in individuals at a heightened risk of GDM can hold particular value, especially during the preconception phase. The alterations in gut microbiota can serve as crucial factors in enhancing lifestyle modifications prior to conception. Further studies are required in this direction to decrease the prevalence of GDM, and efficient measures should be implemented before the consequences appear.

Endothelial dysfunction in psoriatic arthritis patients: correlations between insulin resistance and disease activity.

OBJECTIVE: Cardiovascular atherosclerotic comorbidities represent an important cause of morbidity and mortality in patients diagnosed with psoriatic arthritis. In both atherosclerosis and Psoriatic arthritis, inflammation plays a pivotal role. Psoriatic arthritis is considered as an independent risk factor for the development of atherosclerosis with accelerated evolution. Development of atherosclerosis is initiated by the endothelial cell dysfunction along with inflammation and insulin resistance. The main aim of the study was to evaluate the endothelial function in Psoriatic arthritis patients, and to identify if it is related to the insulin resistance and Psoriatic arthritis disease activity. PATIENTS AND METHODS: In this case-control study, a group of 32 age and gender matched healthy controls was formed and compared to the group of 32 Psoriatic arthritis patients. We assessed the following parameters: Disease Activity in Psoriatic Arthritis Score, Homeostatic Model Assessment for Insulin Resistance, serum levels of the tumor necrosis factor alpha (TNFα), and the endothelial dysfunction by means of the flow-mediated dilation at brachial artery. The Student's t-test, the Pearson correlation and the ANOVA test were used to perform the statistical analysis of the data obtained; p-value <0.05 was considered as statistically significant. RESULTS: Compared to the patients in the control group, TNFα and Homeostatic Model Assessment for Insulin Resistance were increased (p-value <0.001), and flow-mediated dilation at brachial artery was decreased (p-value <0.001) in the disease group. In Psoriatic arthritis patients, significant correlations were found between Disease Activity in Psoriatic Arthritis Score and Homeostatic Model Assessment for Insulin Resistance (r=0.8143, p-value <0.001), and between Disease Activity in Psoriatic Arthritis Score and flow-mediated dilation at brachial artery % (r= -0.8376, p-value <0.001). Psoriatic arthritis patients treated with Methotrexate exhibited reduced values of Disease Activity in Psoriatic Arthritis Score and Homeostatic Model Assessment for Insulin Resistance and increased values of flow-mediated dilation at brachial artery, when compared with the untreated patients. CONCLUSIONS: Endothelial dysfunction is present in Psoriatic arthritis patients and has a significant correlation with both, the course of the disease and the insulin resistance.

Implication of wide surgical excision in minimizing positive margins and consequential secondary excision - a retrospective comparative study involving 106 basal cell carcinoma cases.

OBJECTIVE: The use of current surgical techniques in the management of skin cancers that are not amenable to other treatment options has become the cornerstone of dermatological surgical intervention. Among the many benign lesions and malignant lesions, such as squamous cell carcinomas, melanomas, and Merkel cell carcinomas, the tumors that are commonly excised surgically are the basal cell carcinomas (BCC). Although the majority of BCC lesions spread locally and are rarely metastatic, these lesions may recur, especially, if the excised tissue consists of positive surgical margins. As BCC lesions are more common on the head, face, and neck regions, inadvertent positive margin excisions to help avoid major disfigurement of the regions may contribute to their recurrence. Trichoepithelioma (TE) is a benign tumor that bears a close resemblance to BCC, and therefore, clinicians encounter difficulty in differentiating between TE and BCC lesions. Clinicians have to rely on histopathology and immune-histochemical markers to rule out TE. This differentiation is crucial to make a definitive diagnosis of BCC and subsequently, employ a more aggressive surgical excision approach to treat this invasive tumor as compared with TE. Our focus in this article is to highlight only the surgical excision management of local and or locally invasive BCCs and report the success rate of our hospital's Dermato-venereology clinic (DVC) in Timisoara, Romania. This article highlights the role of an appropriate wide local lesion excision (5 mm) with negative surgical margins in the prevention of further surgical interventions, be it for corrective or esthetic reasons. PATIENTS AND METHODS: This is a retrospective study that summarizes the evaluation of 120 lesions from 106 patients who were treated for BCCs at DVC (University Hospital), using a wide surgical excision method.  Following the Romanian Society of Dermatologists guidelines, local non-aggressive BCC lesions were excised with margins of 5 mm and up to 1 cm for the aggressive sclerosing subtype. RESULTS: The results of the audit of a sample of 120 lesions from 106 patients demonstrated that none of the surgically treated patients had recurrences and only 23 (19.16%) had positive surgical margin lesions. Out of these, 17 (73.91%) lesions underwent second surgical excision, while only three (13.04%) showed the presence of a residual tumor. The evaluation results may encourage dermatologists worldwide to make appropriately sized excision, especially in regions other than the head and neck, to avoid positive surgical margins and eliminate the need for consequent surgery. CONCLUSIONS: For a better post-surgical prognosis of BCC, the authors recommend the practice of a wide margin excision (5 mm) during the primary surgery to avoid secondary surgery, especially if the tissue in the region is not sparse and chances of causing major disfigurement are minimal. As our findings suggest, only a few cases have the presence of residual tumor in the second surgery, hence authors also advocate the necessity to inform the patients about the merits of a second surgery, clearly mentioning the possibility of the absence of tumor even in the presence of positive margin.

Epstein-barr virus regulates c-MYC, apoptosis, and tumorigenicity in Burkitt lymphoma.

Loss of the Epstein-Barr virus (EBV) genome from Akata Burkitt lymphoma (BL) cells is coincident with a loss of malignant phenotype, despite the fact that Akata and other EBV-positive BL cells express a restricted set of EBV gene products (type I latency) that are not known to overtly affect cell growth. Here we demonstrate that reestablishment of type I latency in EBV-negative Akata cells restores tumorigenicity and that tumorigenic potential correlates with an increased resistance to apoptosis under growth-limiting conditions. The antiapoptotic effect of EBV was associated with a higher level of Bcl-2 expression and an EBV-dependent decrease in steady-state levels of c-MYC protein. Although the EBV EBNA-1 protein is expressed in all EBV-associated tumors and is reported to have oncogenic potential, enforced expression of EBNA-1 alone in EBV-negative Akata cells failed to restore tumorigenicity or EBV-dependent down-regulation of c-MYC. These data provide direct evidence that EBV contributes to the tumorigenic potential of Burkitt lymphoma and suggest a novel model whereby a restricted latency program of EBV promotes B-cell survival, and thus virus persistence within an immune host, by selectively targeting the expression of c-MYC.

Assessment of Mitochondrial Dysfunction and Monoamine Oxidase Contribution to Oxidative Stress in Human Diabetic Hearts.

Mitochondria-related oxidative stress is a pathomechanism causally linked to coronary heart disease (CHD) and diabetes mellitus (DM). Recently, mitochondrial monoamine oxidases (MAOs) have emerged as novel sources of oxidative stress in the cardiovascular system and experimental diabetes. The present study was purported to assess the mitochondrial impairment and the contribution of MAOs-related oxidative stress to the cardiovascular dysfunction in coronary patients with/without DM. Right atrial appendages were obtained from 75 patients randomized into 3 groups: (1) Control (CTRL), valvular patients without CHD; (2) CHD, patients with confirmed CHD; and (3) CHD-DM, patients with CHD and DM. Mitochondrial respiration was measured by high-resolution respirometry and MAOs expression was evaluated by RT-PCR and immunohistochemistry. Hydrogen peroxide (H2O2) emission was assessed by confocal microscopy and spectrophotometrically. The impairment of mitochondrial respiration was substrate-independent in CHD-DM group. MAOs expression was comparable among the groups, with the predominance of MAO-B isoform but no significant differences regarding oxidative stress were detected by either method. Incubation of atrial samples with MAOs inhibitors significantly reduced the H2O2 in all groups. In conclusion, abnormal mitochondrial respiration occurs in CHD and is more severe in DM and MAOs contribute to oxidative stress in human diseased hearts with/without DM.

Epstein-Barr virus recombinant lacking expression of glycoprotein gp150 infects B cells normally but is enhanced for infection of epithelial cells.

Glycoprotein gp150 is a highly glycosylated protein encoded by the BDLF3 open reading frame of Epstein-Barr virus (EBV). It does not have a homolog in the alpha- and betaherpesviruses, and its function is not known. To determine whether the protein is essential for replication of EBV in vitro, a recombinant virus which lacked its expression was made. The recombinant virus had no defects in assembly, egress, binding, or infectivity for B cells or epithelial cells. Infection of epithelial cells was, however, enhanced. The glycoprotein was sensitive to digestion with a glycoprotease that digests sialomucins, but no adhesion to cells that express selectins that bind to sialomucin ligands could be detected.

The influence of some antipsychotics on erythrocyte magnesium and plasma magnesium, calcium, copper and zinc in patients with paranoid schizophrenia.

OBJECTIVE: The aim of the study was the investigation of plasma magnesium, calcium, copper and zinc and erythrocyte magnesium levels in patients with paranoid schizophrenia and the influence of the therapy with two antipsychotic drugs (haloperidol and risperidone) on these concentrations. METHODS: We investigated the influence of treatment with haloperidol and risperidoneon plasma and erythrocyte magnesium and on plasmatic levels of zinc, calcium and copper on hospitalized 56 patients diagnosed with paranoid schizophrenia (DSM IV). RESULTS: Our data indicate a decrease of erythrocyte magnesium levels in schizophrenic patients (4.82 +/- 3.1 mg/L vs. 59.2 +/- 1.1 mg/L in control group, p < 0.01). The plasma level of magnesium was unchanged (18.9 +/- 2.17 mg/L in schizophrenic patients vs. 18.26 +/- 1.9 mg/L in control group). CONCLUSIONS: We consider plasma Cu(2+)/erythrocyte Mg(2+) and plasma Cu(2+)/Zn(2+) ratio two important biological markers of the acute paranoid schizophrenia.

[The histopathological study of the bronchopulmonary carcinoma]. / Studiu histopatologic în carcinomul bronhopulmonar.

PURPOSE: The aim of the study is to reveal the predominant histological types of the bronchopulmonary carcinomas diagnosed at the Pneumology Hospital in the period of 1st January 1996-December 31 1998. MATERIAL AND METHODS: The study enclosed 196 cases of CBP, representing 174 men and 22 women with ages between 31 and 78 of years. The studied specimens were pieces of bronchoscopical and surgical biopsies, material obtained from the pneumological clinic. RESULTS AND DISCUSSIONS: The histological analysis revealed the increasing number of the bronchopulmonary carcinoma, mainly to men with mean age of sixty and the predominance of the epidermoid carcinoma (137) and a reduced number of cases of adenocarcinomas (31) and undifferentiated carcinomas (28). The knowing of the histological type of the CBP is very important in the calculation of the prognosis. CONCLUSIONS: Our study demonstrate the predominance of CBP at men (174), with ages between 55 and 65 years (127 cases) and similar incidences for all histological types of CBP comparative with other territories.

Role of heme-hemopexin in human T-lymphocyte proliferation.

Heme-hemopexin supports and stimulates proliferation of human acute T-lymphoblastic (MOLT-3) cells, suggesting the participation of heme in cell growth and division. MOLT-3 cells express approximately 58,000 hemopexin receptors per cell (apparent Kd 20 nM), of which about 20% are on the cell surface. Binding is dose- and temperature-dependent, and growth in serum-free IMDM medium is stimulated by 100-1000 nM heme-hemopexin, consistent with the high affinity of the receptor for hemopexin, and maximal growth is seen in response to 500 nM complex. Growth was similar in defined minimal medium supplemented with either low concentrations of heme-hemopexin or iron-transferrin, and either of these complexes were about 80% as effective as a serum supplement. Heme-hemopexin, but not apo-hemopexin, reversed the growth inhibition caused by desferrioxamine showing that heme-iron derived from heme catabolism is used for cell growth. Cobalt-protoporphyrin (CoPP)-hemopexin, which binds to the receptor but is not transported intracellularly [Smith et al., (1993) J. Biol. Chem. 268, 7365], also stimulated cell proliferation in serum-free IMDM but did not "rescue" the cells from desferrioxamine. Furthermore, CoPP-hemopexin effectively competed for the hemopexin receptor with heme-hemopexin and diminished its growth stimulatory effects. In addition, protein kinase C (PKC) is translocated to the plasma membrane within 5 min after heme-hemopexin is added to the medium, reaches maximum activity within 5-10 min, and declines to unstimulated levels by 30 min. Heme-hemopexin and CoPP-hemopexin both augmented MOLT-3 cell growth stimulated by serum. Thus, heme-hemopexin not only functions as an iron source for T-cells but occupancy of the hemopexin receptor itself triggers signaling pathway(s) involved in the regulation of cell growth. The stimulation of growth of human T-lymphocytes by heme-hemopexin is likely to be a physiologically relevant mechanism at sites of injury, infection, and inflammation.

Epstein-Barr virus gH is essential for penetration of B cells but also plays a role in attachment of virus to epithelial cells.

Entry of Epstein-Barr virus (EBV) into B cells is initiated by attachment of glycoprotein gp350 to the complement receptor type 2 (CR2). A complex of three glycoproteins, gH, gL, and gp42, is subsequently required for penetration. Gp42 binds to HLA class II, which functions as an entry mediator or coreceptor and, by analogy with other herpesviruses, gH is then thought to be involved virus-cell fusion. However, entry of virus into epithelial cells is thought to be different. It can be initiated by attachment by an unknown glycoprotein in the absence of CR2. There is no interaction between gp42 and HLA class II and instead a distinct complex of only the two glycoproteins gH and gL interacts with a novel entry mediator. Again, by analogy with other viruses gH is thought to be critical to fusion. To investigate further the different roles of gH in infection of the two cell types and to examine its influence on the assembly of the gH-gL-gp42 complex, we constructed two viruses, one in which the gH open reading frame was interrupted by a cassette expressing a neomycin resistance gene and the gene for green fluorescent protein and one as a control in which the neighboring nonessential thymidine kinase gene was interrupted with the same cassette. Virus lacking gH exited from cells normally, although loss of gH resulted in rapid turnover of gL and gp42 as well. The virus bound normally to B lymphocytes but could not infect them unless cells and bound virus were treated with polyethylene glycol to induce fusion. In contrast, virus that lacked the gH complex was impaired in attachment to epithelial cells and the effects of monoclonal antibodies to gH implied that this resulted from loss of gH rather than other members of the complex. These results suggest a role for gH in both attachment and penetration into epithelial cells.

Histones of Chlamydomonas reinhardtii. Synthesis, acetylation, and methylation.

Histones of the green alga Chlamydomonas reinhardtii were prepared by a new method and fractionated by reversed-phase high-performance liquid chromatography. Acid-urea-Triton gel analysis and tritiated acetate labeling demonstrated high levels of steady-state acetylation for the single histone H3 protein, in contrast to low levels on histones H4 and H2B. Twenty percent of histone H3 is subject to dynamic acetylation with, on average, three acetylated lysine residues per protein molecule. Histone synthesis in light-dark-synchronized cultures was biphasic with pattern differences between two histone H1 variants, between two H2A variants, and between H2B and ubiquitinated H2B. Automated protein sequence analysis of histone H3 demonstrated a site-specific pattern of steady-state acetylation between 7 and 17% at five of the six amino-terminal lysines and of monomethylation between 5 and 81% at five of the eight amino-terminal lysines in a pattern that may limit dynamic acetylation. An algal histone H3 sequence was confirmed by protein sequencing with a single threonine as residue 28 instead of the serine28-alanine29 sequence, present in all other known plant and animal H3 histones.