Correlation of estrogen receptor beta gene polymorphisms with spinal bone mineral density in peri- and post-menopausal Greek women

Estrogens play a significant role in bone physiology. Their action is mainly exerted through their receptors. Estrogen receptor alpha (ER) plays a major role in bone homeostasis and there is evidence suggesting that estrogen receptor beta (ERβ) has also an effect on BMD.

We investigated the possible effect of two ERβ gene polymorphisms on spinal bone mineral density (BMD) and metabolic bone markers in Greek women.

Spine BMD as well as biochemical bone markers were measured in 147 healthy peri- and post-menopausal women [mean age (S.D.) 54 (7.9) years]. Genotyping was performed for two restriction fragment length polymorphisms (RFLPs) of ERβ gene, RsaI in exon 5 and AluI in exon 8. For each polymorphism studied the cohort was divided into two groups: the “wild-type” group (RR and AA, respectively) and the “carrier” group including subjects with at least one allele with the restriction site (Rr&rr and Aa&aa, respectively).

The distribution of RsaI genotypes was RR: 91.2% (n = 134), Rr: 8.2% (n = 12), and rr: 0.6% (n = 1) and of AluI genotypes AA: 36.7% (n = 54), Aa: 57.2% (n = 84), and aa: 6.1% (n = 9). No linkage disequilibrium was found between the two polymorphic sites studied. Spine BMD did not differ significantly in the two groups of either polymorphism, after adjusting for age, weight, height, and years since menopause [mean BMD (S.D.) for RR 0.841 (0.17) g/cm² versus Rr&rr 0.798 (0.13) g/cm², p = 0.25, and mean BMD (S.D.) for AA 0.828 (0.16) g/cm² versus Aa&aa 0.848 (0.17) g/cm², p = 0.32]. No significant differences were noted in metabolic bone markers except for a marginal difference of RR versus Rr/rr in urinary hydroxyproline/creatinine ratio [median (IQR) 3.88 (6.04) μmol/mmol in RR versus 8.2 (4.32) μmol/mmol in Rr/rr, p = 0.05]. Furthermore, no interaction between the two polymorphisms on BMD was found.

In conclusion, in a Greek female post-menopausal population, the two ERβ gene polymorphisms were not associated with BMD, or metabolic bone markers.     

Apolipoprotein E polymorphism is not associated with spinal bone mineral density in peri- and postmenopausal Greek women

OBJECTIVES: A number of studies have shown a positive relation between ApoE gene and osteoporosis or fracture risk but this finding has not been uniform in all populations studied. The aim of the present study was to determine the possible effect of ApoE gene polymorphism on spinal bone mineral density and metabolic bone markers in Greek women. METHODS: One hundred and forty-seven healthy peri- and postmenopausal women (mean age 54.3 +/- 7.8 years) participated in the study. In all participants, ApoE gene genotype was determined and spinal bone mineral density (BMD) as well as biochemical bone markers were measured. The ApoE genotypes distribution was 0.7% (n = 1) for E2/2, 5.4% (n = 8) for E2/3, 2% (n = 3) for E2/4, 73.5% (n = 108) for E3/3, 16.3% (n = 24) for E3/4 and 2% (n = 3) for E4/4. Participants were divided in two groups according to the presence of the E4 haplotype: E4 carriers (n = 30) and E4 non-carriers (n = 117). RESULTS: Spinal BMD was similar in the two groups, after adjusting for age, weight, height and years since menopause (mean +/- S.D., 0.835 +/- 0.16 g/cm2 in E4 non-carriers versus 0.831 +/- 0.16 g/cm2 in E4 carriers, P = 0.99). Serum osteocalcin levels did not differ significantly in the two groups (median (interquartile range, IQR), 0.55 (0.58) nmol/l in E4 non-carriers versus 0.51 (0.43) nmol/l in E4 carriers), whereas urinary hydroxyproline/creatinine ratio was significantly higher in the E4 non-carriers group (median (IQR), 5.18 (6.04) micromol/mmol in E4 non-carriers versus 1.73 (3.45) micromol/mmol in E4 carriers, P < 0.01). Urinary pyridinoline/creatinine and deoxypyridinoline/creatinine ratios, measured in a subgroup of 51 women, were similar between ApoE carriers and non-carriers, respectively (median (IQR), 25.1 (9.3) nmol/mmol in E4 non-carriers versus 21.8 (7) nmol/mmol in E4 carriers and 6.7 (3.1) nmol/mmol in E4 non-carriers versus 7 (2.2) nmol/mmol in E4 carriers). CONCLUSION: In conclusion, in a Greek female postmenopausal population, ApoE gene does not seem to play an important role in determining BMD and neither does it affect the majority of metabolic bone markers.     

Lab-on-a-chip synthesis of inorganic nanomaterials and quantum dots for biomedical applications

The past two decades have seen a dramatic raise in the number of investigations leading to the development of Lab-on-a-Chip (LOC) devices for synthesis of nanomaterials. A majority of these investigations were focused on inorganic nanomaterials comprising of metals, metal oxides, nanocomposites and quantum dots. Herein, we provide an analysis of these findings, especially, considering the more recent developments in this new decade. We made an attempt to bring out the differences between chip-based as well as tubular continuous flow systems. We also cover, for the first time, various opportunities the tools from the field of computational fluid dynamics provide in designing LOC systems for synthesis inorganic nanomaterials. Particularly, we provide unique examples to demonstrate that there is a need for concerted effort to utilize LOC devices not only for synthesis of inorganic nanomaterials but also for carrying out superior in vitro studies thereby, paving the way for faster clinical translation. Even though LOC devices with the possibility to carry out multi-step syntheses have been designed, surprisingly, such systems have not been utilized for carrying out simultaneous synthesis and bio-functionalization of nanomaterials. While traditionally, LOC devices are primarily based on microfluidic systems, in this review article, we make a case for utilizing millifluidic systems for more efficient synthesis, bio-functionalization and in vitro studies of inorganic nanomaterials tailor-made for biomedical applications. Finally, recent advances in the field clearly point out the possibility for pushing the boundaries of current medical practices towards personalized health care with a vision to develop automated LOC-based instrumentation for carrying out simultaneous synthesis, bio-functionalization and in vitro evaluation of inorganic nanomaterials for biomedical applications.     

The long-term effectiveness of generic adult fixed-dose combination antiretroviral therapy for HIV-infected Ugandan children

Background

Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs.

Objective

To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment.

Methods

Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation.

Results

From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7–13.9) and 348,846copies/mL (IQR 160,941–681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10–8.32), p=0.03}; no difference was found among those with CD4 cell percent >5–14.9% and <5%.

Conclusion

Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success.     

Utility of dystrophin and utrophin staining in childhood muscular dystrophy

To determine the utility of dystrophin and utrophin staining in the differential diagnosis of childhood muscular dystrophy. Fifty muscle biopsies of histologically confirmed cases of childhood muscular dystrophy, below 16 years of age, were stained immunohistochemically for dystrophin and utrophin. All the 30 muscle biopsies of patients with Duchenne muscular dystrophy (DMD) showed all or majority of muscle fibers deficient for dystrophin and positive for utrophin. In the 4 female DMD carriers there was mosaic pattern of staining for dystrophin and reciprocal positivity for utrophin. All the muscle biopsies of patients with other childhood onset muscular dystrophies were positive for dystrophin and negative for utrophin. This study shows that dystrophin staining differentiates DMD and DMD carriers from other childhood muscular dystrophies and utrophin staining is of no added value. Utrophin up-regulation may compensate for structural deficiency in dystrophic muscle.     

Awake Craniotomy for Tumour Excision

Background

Craniotomy and excision of tumours can produce neurological deficits if the tumour is located close to eloquent areas of the brain. One technique of overcoming this problem is to keep the patient ‘awake’ during surgery.

Methods

Eight patients with intra cranial space occupying lesions (ICSOL) were operated ‘awake’, using a combination of skull block with sedation and analgesia. A mixture of 0.125% bupivacaine and 0.5% lignocaine was used for various nerve and field blocks. Midazolam, fentanyl and propofol in titrated doses were used to achieve conscious sedation.

Result

The procedure was successful in all the patients. They tolerated the procedure well and were able to follow the commands intraoperatively as desired. There were no significant complications.

Conclusion

Awake craniotomy with skull blocks with sedation and analgesia is a well established procedure. It requires a good rapport between surgeon, anaesthesiologist and the patient.Key Words: Awake craniotomy, Skull block, Sedation, Analgesia