Volumetric evaluation of the relations among the cerebrum,cerebellum and brain stem in young subjects: a combination of stereology and magnetic resonance imaging

The Cavalieri estimator using a point grid is used to estimate the volume of three-dimensional structures based on two-dimensional slices of the object. The size of the components of intracranial neural structures should have proportional relations among them. The volume fraction approach of stereological methods provides information about volumetric relations of the components of structures. The purpose of our study is to estimate the volume and volume fraction data related to the cerebrum, cerebellum and brain stem. In this study, volume of the total brain, cerebrum, cerebellum and brain stem were estimated in 24 young Turkish volunteers (12 males and 12 females) who are free of any neurological symptoms and signs. The volume and volume fraction of the total brain, cerebrum, cerebellum and brain stem were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods. The mean (+/-SD) total brain, cerebrum and cerebellum volumes were 1,202.05 +/- 103.51, 1,143.65 +/- 106.25 cm(3) in males and females, 1,060.0 +/- 94.6, 1,008.9 +/- 104.3 cm(3 )in males and females, 117.75 +/- 10.7, 111.83 +/- 8.0 cm(3) in males and females, respectively. The mean brain stem volumes were 24.3 +/- 2.89, 22.9 +/- 4.49 cm(3) in males and females, respectively. Our results revealed that female subjects have less cerebral, cerebellar and brain stem volumes compared to males, although there was no statistically significant difference between genders (P > 0.05). The volume ratio of the cerebrum to total brain volume (TBV), cerebellum to TBV and brain stem to TBV were 88.16 and 88.13% in males and females, 9.8 and 9.8% in males and females, 2.03 and 2.03% in males and females, respectively. The volume ratio of the cerebellum to cerebrum, brain stem to cerebrum and brain stem to cerebellum were 11.12 and 11.16% in males and females, 2.30 and 2.31% in males and females, 20.7 and 20.6% in males and females, respectively. The difference between the genders was not statistically significant (P > 0.05). Our results revealed that the volumetric composition of the cerebrum, cerebellum and brain stem does not show sexual dimorphism.     

Critical role of multidrug efflux pump CmeABC in bile resistance and in vivo colonization of Campylobacter jejuni

CmeABC functions as a multidrug efflux pump contributing to the resistance of Campylobacter to a broad range of antimicrobials. In this study, we examined the role of CmeABC in bile resistance and its contribution to the adaptation of Campylobacter jejuni in the intestinal tract of the chicken, a natural host and a major reservoir for Campylobacter. Inactivation of cmeABC drastically decreased the resistance of Campylobacter to various bile salts. Addition of choleate (2 mM) in culture medium impaired the in vitro growth of the cmeABC mutants but had no effect on the growth of the wild-type strain. Bile concentration varied in the duodenum, jejunum, and cecum of chicken intestine, and the inhibitory effect of the intestinal extracts on the in vitro growth of Campylobacter was well correlated with the total bile concentration in the individual sections of chicken intestine. When inoculated into chickens, the wild-type strain colonized the birds as early as day 2 postinoculation with a density as high as 10(7) CFU/g of feces. In contrast, the cmeABC mutants failed to colonize any of the inoculated chickens throughout the study. The minimum infective dose for the cmeABC mutant was at least 2.6 x 10(4)-fold higher than that of the wild-type strain. Complementation of the cmeABC mutants with a wild-type cmeABC allele in trans fully restored the in vitro growth in bile-containing media and the in vivo colonization to the levels of the wild-type strain. Immunoblotting analysis indicated that CmeABC is expressed and immunogenic in chickens experimentally infected with C. jejuni. Together, these findings provide compelling evidence that CmeABC, by mediating resistance to bile salts in the intestinal tract, is required for successful colonization of C. jejuni in chickens. Inhibition of CmeABC function may not only control antibiotic resistance but also prevent the in vivo colonization of pathogenic Campylobacter.     

Desflurane anaesthesia in a patient with multiple sclerosis in total hip replacement

Multiple sclerosis (MS) is a progressive demyelinating disease presenting with a relapsing-remitting course and affects large areas of the brain and the spinal cord. Surgical stress often induces exacerbation of MS symptoms. It is mandatory to prepare the MS patient very carefully for the surgery and anaesthesia with an effective premedication and an effective postoperative analgesia following a safe and minimal-risk anaesthesia management. In recent reports, results of general and regional anaesthesia in MS patients have been discussed. To our knowledge this is the first case report of the use of desflurane anaesthesia in a patient with MS. In conclusion, desflurane anaesthesia is a safe and useful method for MS patients.     

Accessory cardiac bronchus and tracheal bronchus anomalies: CT-bronchoscopy and CT-bronchography findings

Most common developmental anomalies of bronchial tree include accessory cardiac bronchus (ACB) and tracheal bronchus (TB). Minor bronchial anomalies include variants of TB, displaced segmental bronchi, and bronchial agenesis. We present CT-bronchoscopy and CT-bronchography findings of three cases with either ACB or TB. Recognition of these anomalies is important, as associated clinical complications, including recurrent episodes of infection, hemoptysis, and perhaps malignancies may be anticipated in a small percentage of patients.     

Acute effect of intranasal estrogen on cerebral and cerebellar perfusion in postmenopausal women

OBJECTIVES: Estrogen action in the brain influences many neurochemical processes. The aim of the study was to evaluate the acute effect of intranasal 17beta-estradiol on cerebral and cerebellar perfusion in postmenopausal women. METHODS: The study group included 24 healthy postmenopausal women who had been in natural menopause for at least 1 year (mean age: 47.38+/-5.9 years). We conducted an experimental, randomized, placebo-controlled, cross-over, double-blind study. Cerebral and cerebellar perfusion was measured after placebo (saline serum physiologic) or intranasal 17beta-estradiol administration by Single Photon Emission Computed Tomography (SPECT) using technetium-99m-hexamethylpropylene amine oxime (Tc99m-HMPAO). Regions of interest (ROIs) were drawn manually. Cerebral and cerebellar perfusions were calculated for each ROI using average number of counts per pixel. Semiquantitative analysis was performed in bilateral frontal, temporal, parietal and occipital lobes, thalamus, putamen, hippocampus, amygdala, caudate nuclei, cerebellar region, anterior/posterior of cingulate gyrus and pons. RESULTS: After intranasal 17beta-estradiol administration, SPECT study revealed significant increases in cerebral and cerebellar perfusion compared to placebo measurements in all studied slices (p<0.05). There was a positive correlation between serum estrogen levels after 17beta-estradiol and cerebral and cerebellar perfusion. CONCLUSIONS: Administration of single dose intranasal 17beta-estradiol increases cerebral and cerebellar perfusions in healthy postmenopausal women.     

Dual neutralization of TNFR-2 and MMP-2 regulates the severity of <Emphasis Type="Italic">S. aureus</Emphasis> induced septic arthritis correlating alteration in the level of interferon gamma and interleukin-10 in terms of TNFR2 blocking

Severity of S. aureus septic arthritis is correlated to prolonged inflammation by inflammatory cytokines like TNF-α, IL-1β, and IL-6 even after successful elimination of bacteria. Role of TNF-α via TNFR2 is not well established in this aspect. IFN-γ induces TNF-α release from the macrophages augmenting the inflammatory arthritis. IL-10 modulates the levels of pro-inflammatory cytokines promoting resolution of inflammation. TNF-α-TNFR2 signaling upregulates both of these cytokines. Higher level of MMP-2 induction by inflammatory cytokines during arthritis promotes tissue destruction. Whether dual neutralization of TNFR-2 and MMP-2 regulates the severity of S. aureus arthritis by modulating local and systemic cytokine milieu mainly due to TNFR-2 blocking was an obvious question. Here, we attempted the effects of neutralization of MMP-2 and TNFR2 on S. aureus arthritis and its impact on pro-inflammatory cytokines and some other parameters related to tissue destruction. Reduction in arthritis index was noticed in infected mice treated with both MMP-2 inhibitor and TNFR2 antibody. Lowest levels of inflammatory cytokines, iNOS, RANKL, NF-κb, JNK kinase, ROS, and MPO, and lysozyme activity were observed in combined neutralization group at 9 and 15 dpi, but at 3 dpi, most of the above parameters remained elevated due to TNFR2 neutralization. Diminished IL-10 and IFN-γ levels as a result of TNFR2 neutralization at early and later phase of infection respectively might be responsible for these contrasting effects. Overall, it can be suggested that administration of MMP-2 inhibitor and TNFR2 antibody in combination is protective against the inflammation and tissue destruction associated with S. aureus infection during the arthritic episode.     

Effect of vitamin D deficiency on the 75 g oral glucose tolerance test screening and insulin resistance

Abstract

Gestational diabetes mellitus (GDM), is the most common medical complications of pregnancy. This study aimed to clarify the effect of second-trimester vitamin D deficiency on the 75?g oral glucose tolerance test (OGTT) screening and insulin resistance. A total of 120 pregnant women with a singleton pregnancy at a gestational age of 26–28?weeks were analyzed. Participants were divided into two groups according to 25-hydroxyvitamin D levels; vitamin D deficiency, and control groups. For GDM scan, 75?g OGTT was preferred. GDM prevalence was 17.5% in vitamin D deficiency group and 13.75% in control group, there is no significant difference in GDM prevalence (p?=?0.149). Fasting plasma glucose and 1-h plasma glucose levels were significantly higher in the vitamin D deficiency group than in the control group (p?<?.001 and p?<?.001, respectively). No significant differences were observed between 2-hour plasma glucose levels (p?=?.266). The HOMA-IR level was significantly higher in the vitamin D deficiency group than in the control group (p?<?.001). The findings of the present study suggested that vitamin D deficiency in the second trimester was inversely correlated with fasting and 1-h plasma glucose after 75?g glucose challenge test; also, low 25 OHD₃ levels were associated with insulin resistance.     

Histological findings of long-term healing of the experimental defects by application of a synthetic biphasic ceramic in rats

Calcium phosphate ceramics are generally biocompatible and can develop interactions with human recipient bone. Therefore, they can be widely used in the field of periodontology and dentistry. The purpose of this investigation was to assess the long-term histological bone healing results of experimentally created critical size parietal bone defects in rats. Twelve Wistar rats were used in this investigation. Two 6-mm wide, symmetrical, and circular critical size defects were created in each parietal bone of the animals. While the right defects filled with granular implant (Ceraform), the symmetrical defects were taken as controls. Eighteen months after implantation, rats were killed and defects including the biomaterial with surrounding bone was taken for histological examination. Serial histological sections were cut across the defects and stained for the histological analysis. Both control and Ceraform implanted regions contained dense collagenous tissue. In the implantation site, multinuclear giant cells were observed around the material. On the other hand, there were no necrosis, tumour, and infection in the implantation region. There was no statistical difference between the control and ceraform implanted groups when the bone formation results were compared (p > 0.05). In conclusion, the results revealed that this material is biocompatible and does enhance the new bone building despite the long-term observation period. Although this biphasic ceramic shows within the limits of the study as a less resorptive and not osteoconductive properties, it can be considered as a biocompatible bone defect filling material having a limited application alternative in dentistry and medicine.     

Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow

Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1α are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin–biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK⁺ cells was 236 (range, 20–847) per 5 × 10⁴ enriched BM cells. The presence of CK⁺ cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK⁺ per 5 × 10⁴ enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.     

Newborn screening for neurodevelopmental diseases: Are we there yet?

In the US, newborn screening (NBS) is a unique health program that supports health equity and screens virtually every baby after birth, and has brought timely treatments to babies since the 1960's. With the decreasing cost of sequencing and the improving methods to interpret genetic data, there is an opportunity to add DNA sequencing as a screening method to facilitate the identification of babies with treatable conditions that cannot be identified in any other scalable way, including highly penetrant genetic neurodevelopmental disorders (NDD). However, the lack of effective dietary or drug-based treatments has made it nearly impossible to consider NDDs in the current NBS framework, yet it is anticipated that any treatment will be maximally effective if started early. Hence there is a critical need for large scale pilot studies to assess if and how NDDs can be effectively screened at birth, if parents desire that information, and what impact early diagnosis may have. Here we attempt to provide an overview of the recent advances in NDD treatments, explore the possible framework of setting up a pilot study to genetically screen for NDDs, highlight key technical, practical, and ethical considerations and challenges, and examine the policy and health system implications.