Does Diet‐Induced Weight Loss Lead to Bone Loss in Overweight or Obese Adults? A Systematic Review and Meta‐Analysis of Clinical Trials

Diet‐induced weight loss has been suggested to be harmful to bone health. We conducted a systematic review and meta‐analysis (using a random‐effects model) to quantify the effect of diet‐induced weight loss on bone. We included 41 publications involving overweight or obese but otherwise healthy adults who followed a dietary weight‐loss intervention. The primary outcomes examined were changes from baseline in total hip, lumbar spine, and total body bone mineral density (BMD), as assessed by dual‐energy X‐ray absorptiometry (DXA). Secondary outcomes were markers of bone turnover. Diet‐induced weight loss was associated with significant decreases of 0.010 to 0.015 g/cm² in total hip BMD for interventions of 6, 12, or 24 (but not 3) months' duration (95% confidence intervals [CIs], –0.014 to –0.005, –0.021 to –0.008, and –0.024 to –0.000 g/cm², at 6, 12, and 24 months, respectively). There was, however, no statistically significant effect of diet‐induced weight loss on lumbar spine or whole‐body BMD for interventions of 3 to 24 months' duration, except for a significant decrease in total body BMD (–0.011 g/cm²; 95% CI, –0.018 to –0.003 g/cm²) after 6 months. Although no statistically significant changes occurred in serum concentrations of N‐terminal propeptide of type I procollagen (P1NP), interventions of 2 or 3 months in duration (but not of 6, 12, or 24 months' duration) induced significant increases in serum concentrations of osteocalcin (0.26 nmol/L; 95% CI, 0.13 to 0.39 nmol/L), C‐terminal telopeptide of type I collagen (CTX) (4.72 nmol/L; 95% CI, 2.12 to 7.30 nmol/L) or N‐terminal telopeptide of type I collagen (NTX) (3.70 nmol/L; 95% CI, 0.90 to 6.50 nmol/L bone collagen equivalents [BCEs]), indicating an early effect of diet‐induced weight loss to promote bone breakdown. These data show that in overweight and obese individuals, a single diet‐induced weight‐loss intervention induces a small decrease in total hip BMD, but not lumbar spine BMD. This decrease is small in comparison to known metabolic benefits of losing excess weight. © 2015 American Society for Bone and Mineral Research     

Analysis of interphase cells for the Philadelphia translocation using painting probe made by inter-Alu-polymerase chain reaction from a radiation hybrid

Fluorescence in situ hybridization (FISH) probe for the identification of the Philadelphia (Ph) translocation [t(9;22) (q34;q11)] in chronic myelogenous leukemia cells was developed by inter-Alu-polymerase chain reaction of DNA from an interspecific somatic cell hybrid containing approximately 5 Mb of human DNA covering the ABL gene region on human chromosome 9q34. This probe was large enough to be effective in identifying the genomic domains yet small enough to resolve them in more than 90% of bone marrow interphase cells. Combination of the probe with a cosmid contig probe for the BCR region of chromosome 22 in two- color FISH reduced the frequency of false-positive identification of the Ph chromosome to less than 1%. The procedure allows detection of as few as 1% Ph+ cells independent of the cycling status or BCR/ABL expression level of cells, and the quantitation of non-Ph chromosome- containing interphase nuclei in the marrow of patients judged 100% Ph+ by standard cytogenetics.     

Reply: Which is more counterproductive: a brief delay or 'start anyway'?

Sir, Thank you for inviting us to respond to El-Toukhy and Taranissi’scomments upon our paper (Abdalla and Thum, 2006). We providea 7-day-a-week clinical service in our unit and could easilymeasure early follicular phase FSH levels for all patients.Indeed, as it is equally valid to measure the FSH on day 1,2 or 3, any     

Repeated testing of basal FSH levels has no predictive value for IVF outcome in women with elevated basal FSH

BACKGROUND: It is a common practice to repeatedly test the level of basal FSH early in the cycle and to start IVF treatment only when the FSH level is below a certain threshold value. This is based on the idea that these women will respond better to ovarian stimulation when the basal FSH level is lower at the start of the cycle. The aim of this study is to assess the value of this practice. METHODS: Between January 1995 and January 2003, 39 women were identified. These women underwent two IVF treatment cycles within a 12 month period. The basal FSH level prior to each of these cycles was known to have changed. The treatment cycles were divided into cycles with a high basal FSH (> or =10 IU/l) and cycles with a low basal FSH (<10 IU/l). RESULTS: The 39 women underwent a total of 78 treatment cycles (in the first cycle 20 had elevated level of FSH and 19 had low FSH and vice versa in the second cycle). Therefore, there were 39 cycles with high FSH and 39 cycles with low FSH. There was obviously no live birth in the first treatment cycle, hence the reason for the patient undergoing another treatment cycle within 12 months of the first one. In the high FSH group, six became pregnant [pregnancy rate (PR) = 15.4%] and five delivered [live birth rate (LBR) = 12.8%]. In the low FSH group, three became pregnant (PR = 7.7%) and two delivered (LBR = 5.1%). The difference in PR and LBR, however, was not significant. Neither were there significant differences between the two groups with regard to the number of oocytes collected, oocytes fertilized, embryos transferred or miscarriage rate. CONCLUSION: The results of this study reveal that women who are poor responders or with reduced ovarian reserve have a poor outcome and repeatedly testing them will add no value. Cycling women with a history of elevated FSH should be offered treatment without further delay. Delaying treatment for these women could be counterproductive, as they may have to wait for many months, during which time they are getting older and closer to their menopause.     

Elevated basal FSH and embryo quality: lessons from extended culture embryos

Background  The relationship between elevated basal FSH and embryo quality remains a topic of heated discussion among practitioners of ART. Some authors suggest a negative effect of raised FSH on the quality of embryos and therefore on IVF treatment outcome. We postulate that women with elevated FSH who respond well to ovarian stimulation and have embryos to transfer, have the same chance of conceiving like women of a similar age with normal FSH. To test this hypothesis, we studied women with elevated basal FSH who made enough embryos to qualify for blastocyst culture and day 5 embryo transfer. Methods  Analysis of data collected prospectively, on women age 25–43 years, who underwent IVF between January 2005 and December 2006. The women were divided into: those with high FSH (≥10 IU/L) and women with normal FSH (<10 IU/L). We analysed data to show treatment outcome in the two groups, following embryo transfer on day 3 and after transfer on day 5. Outcome measures include number of oocytes retrieved, number of embryos available, implantation rate, pregnancy and live birth rate. Results  Among the 1,858 women who under-went a day 3 transfer, 1,368 had basal FSH ≤ 10 IU/L, and in 492 basal FSH was above 10 IU/L. The average number of oocytes retrieved was lower among women with elevated FSH (10.12 ± 5.6 Vs 6.16 ± 3.9). Women with a normal FSH, had a higher pregnant and live birth rate than those with elevated FSH (43.3% vs 27.9% p = 0.021) and (30.8% vs 17.6% p = 0.028) respectively. 398 women made enough embryos to qualify for extended embryo culture to blastocysts. Of these 366 had an FSH ≤ 10 IU/L and 32 had FSH > 10 IU/L. In this group, there was no significant difference in the pregnancy and live birth rates between women with elevated and those with normal FSH, (67.2% vs 65.6%) and (51.9% vs 43.8%) respectively. In this selected group of women where quantity is not an issue, the quality of embryos was same irrespective of whether the basal FSH was low or high. Conclusion  Women with elevated basal FSH who respond well to stimulation and generate a good number of oocytes / embryos have a chance of becoming pregnant and having a live birth similar to that of women of their age. Women should therefore not be denied the benefits of IVF based solely on the basal FSH level as a subset may respond well and therefore have a good chance of taking home a baby.     

The Role of Dopamine in Drosophila Larval Classical Olfactory Conditioning

Learning and memory is not an attribute of higher animals. Even Drosophila larvae are able to form and recall an association of a given odor with an aversive or appetitive gustatory reinforcer. As the Drosophila larva has turned into a particularly simple model for studying odor processing, a detailed neuronal and functional map of the olfactory pathway is available up to the third order neurons in the mushroom bodies. At this point, a convergence of olfactory processing and gustatory reinforcement is suggested to underlie associative memory formation. The dopaminergic system was shown to be involved in mammalian and insect olfactory conditioning. To analyze the anatomy and function of the larval dopaminergic system, we first characterize dopaminergic neurons immunohistochemically up to the single cell level and subsequent test for the effects of distortions in the dopamine system upon aversive (odor-salt) as well as appetitive (odor-sugar) associative learning. Single cell analysis suggests that dopaminergic neurons do not directly connect gustatory input in the larval suboesophageal ganglion to olfactory information in the mushroom bodies. However, a number of dopaminergic neurons innervate different regions of the brain, including protocerebra, mushroom bodies and suboesophageal ganglion. We found that dopamine receptors are highly enriched in the mushroom bodies and that aversive and appetitive olfactory learning is strongly impaired in dopamine receptor mutants. Genetically interfering with dopaminergic signaling supports this finding, although our data do not exclude on naïve odor and sugar preferences of the larvae. Our data suggest that dopaminergic neurons provide input to different brain regions including protocerebra, suboesophageal ganglion and mushroom bodies by more than one route. We therefore propose that different types of dopaminergic neurons might be involved in different types of signaling necessary for aversive and appetitive olfactory memory formation respectively, or for the retrieval of these memory traces. Future studies of the dopaminergic system need to take into account such cellular dissociations in function in order to be meaningful.     

Cytochrome P450 mono-oxygenase gene expression and protein activity in cultures of adult cardiomyocytes of the rat

There are a substantial number of drugs acting either directly or indirectly on the heart, but surprisingly, little is known about the metabolic capacity of heart muscle cells. We therefore investigated the gene expression and protein activity of cytochrome P450 isozymes in cultures of adult cardiomyocytes of the rat. Semi-quantitative CYP gene expression pattern suggests CYP1A1 and CYP2B1/2 to be key players in cardiomyocytes and upon treatment with Aroclor 1254 approximate 4 fold inductions could be observed for both gene families, when compared with appropriate controls. The mRNA expression of most genes was sustained for prolonged periods of time, e.g. up to 120 h in culture and in the case of the CYP3A1 gene an approximate 10 fold induction was observed at the higher Aroclor 1254 dose level (10 microM) in 24 h old cultures. The constitutively expressed genes, e.g. CYP2C11 and CYP2E1 are expressed throughout the entire culture period (5 days) and did not respond to Aroclor 1254 treatment. CYP4A1 was mainly expressed in freshly isolated cardiomyocytes of control animals and its expression declined rapidly in culture. There was good agreement between gene expression and translated protein activity using 7-ethoxyresorufin and testosterone as substrates. The data reported herein should foster the routine use of freshly isolated and cultivated cardiomyocytes for drug profiling and toxicity studies.