Longitudinal study of the frequency and duration of breastfeeding in rural Bangladeshi women.

A 27-month longitudinal study of 140 Bangladeshi mothers living in three tea gardens examined the effect of maternal factors (mother's age, number of live births, birth interval, and mother's work status) and sex of the infant on the duration and bout frequency of breastfeeding over 8-hr daytime periods. Prolonged breastfeeding of the infant was observed, but there was a sharp decline in duration of breastfeeding over the first 6 months, followed by a more gradual diminution thereafter. The feeding bouts showed a different pattern, with a more gradual decline over time. Housewives consistently showed a greater duration and bout frequency than women in paid employment as tea-pluckers. Over the first 6 months, primigravid mothers breastfed more frequently, but not thereafter. Older mothers (>35 years of age) breastfed with higher frequency during the first 2 months, but thereafter, the bout frequency decreased with increasing age of the infant. Over the 27-month study, maternal work status was the main factor associated with the duration and frequency of breastfeeding, with significantly higher frequency and duration among housewives. However, in the first 6 months after birth, there was very little difference in frequency or duration of breastfeeding between tea-workers and housewives, indicating that working mothers probably adjusted their time to breastfeed their infants before going, or after coming back, from work.     

Effects of atorvastatin on arterial endothelial function in coronary bypass surgery

Objective: Endothelial dysfunction represents a critical early component of organ injury following cardiopulmonary bypass. Recent studies demonstrate that the treatment with atorvastatin is associated with a significant improvement of endothelial function independently of its efficacy on cholesterol levels. Therefore, we investigated the effects of preoperative atorvastatin treatment on endothelium function after coronary surgery. Methods: Forty patients undergoing coronary surgery were randomized to treatment with atorvastatin (20 mg/die; N = 20) or placebo (N = 20) 3 weeks before surgery. Twenty normal patients served as control group. The flow-mediated dilations (FMD) of the brachial artery after both reactive hyperemia (endothelium dependent) and nitroglycerin administration (endothelium independent) were evaluated at baseline, at 48 h, and 5 days postoperatively. Results: At baseline, the endothelium-dependent FMD was significantly attenuated in coronary versus normal patients (normal 10.3 ± 1.8% vs coronary 4.1 ± 1.6%, p < 0.01). At 48 h postoperatively all patients exhibited a reduced FMD compared with baseline values: the endothelium-dependent dilatation showed a drop of 60.1 + 15% in the patients of the placebo group compared with 45.8 + 16.6% (p < 0.05) those in the atorvastatin group. At the univariate analysis, no significant correlation was found between serum levels of either total cholesterol or HDL cholesterol and FMD. The nitroglycerin-induced dilation was not significantly influenced by extracorporeal circulation as well as by atorvastatin treatment. Conclusions: The endothelial dysfunction following cardiopulmonary bypass is improved by the treatment with atorvastatin, by a mechanism unrelated to the drug efficacy of controlling serum cholesterol levels.     

A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in Wolf-Hirschhorn syndrome

A total of five Wolf-Hirschhorn syndrome (WHS) patient with a 4p16.3 de novo microdeletion was referred because of genotype-phenotype inconsistencies, first explained as phenotypic variability of the WHS. The actual deletion size was found to be about 12 Mb in three patients, 5 Mb in another one and 20 Mb in the last one, leading us to hypothesize the presence of an extrachromosome segment on the deleted 4p. A der(4)(4qter --> p16.1::8p23 --> pter) chromosome, resulting from an unbalanced de novo translocation was, in fact, detected in four patients and a der(4)(4qter --> q32::4p15.3 --> qter) in the last. Unbalanced t(4;8) translocations were maternal in origin, the rec(4p;4q) was paternal. With the purpose of verifying frequency and specificity of this phenomenon, we investigated yet another group of 20 WHS patients with de novo large deletions (n = 13) or microdeletions (n = 7) and with apparently straightforward genotype-phenotype correlations. The rearrangement was paternal in origin, and occurred as a single anomaly in 19 out of 20 patients. In the remaining patient, the deleted chromosome 4 was maternally derived and consisted of a der(4)(4qter --> 4p16.3::8p23 --> 8pter). In conclusions, we observed that 20% (5/25) of de novo WHS-associated rearrangements were maternal in origin and 80% (20/25) were paternal. All the maternally derived rearrangements were de novo unbalanced t(4;8) translocations and showed specific clinical phenotypes. Paternally derived rearrangements were usually isolated deletions. It can be inferred that a double, cryptic chromosome imbalance is an important factor for phenotypic variability in WHS. It acts either by masking the actual deletion size or by doubling a quantitative change of the genome.     

Anti-MOG autoantibodies in Italian multiple sclerosis patients: specificity, sensitivity and clinical association

There is considerable evidence that multiple sclerosis (MS) is an immune-mediated disease characterized by infiltration of inflammatory cells into the CNS and demyelination. Several myelin proteins may be encephalitogenic, including myelin basic protein, proteolipid protein and myelin oligodendrocyte glycoprotein (MOG), the latter being expressed on the external layer of myelin sheaths and hence accessible to antibody attack. We investigated MOG autoreactivity in serum and cerebrospinal fluid (CSF) by ELISA, employing the recombinant extracellular domain of MOG as antigen. We tested serum samples from 262 MS patients (175 relapsing-remitting, 43 primary progressive and 44 secondary progressive), 131 patients with other neurological diseases (OND) and 307 healthy controls. No patients or controls were receiving immunomodulating treatments. We found anti-MOG antibodies in the serum of 13.7% MS patients, mainly in those with secondary progressive MS (25%), in 13.7% of OND patients and in 6.2% of controls. We found a direct correlation (R(2) = 0.6, P = 0.002) between disease severity and anti-MOG titer only in patients with primary and secondary progressive MS. Anti-MOG antibodies were present in the CSF of 11.4% MS patients and 18.9% OND patients. Intrathecal synthesis of anti-MOG antibodies was demonstrated in four (4.5%) of MS patients and no OND patients. Anti-MOG antibodies are not specific for MS; however, they may characterize a subset of MS patients and this may be revealed by serial assays in relation to changing disease phase.     

Fibroblast growth factor receptor-1 and neonatal compensatory lung growth after exposure to 95% oxygen

Neonatal rats exposed to 95% oxygen (O2) for 7 days from birth had inhibited lung growth, DNA synthesis, and secondary septation. These parameters were rapidly restored by a period of recovery in air. Northern and Western blot analysis and immunohistochemistry were used to screen for the fibroblast growth factor receptor-1 (FGF-R1) and its high affinity ligand, basic fibroblast growth factor (bFGF), which could have a role in this recovery process. Expression of bFGF in the lung was significantly reduced at the end of the 7-day exposure to 95% O2 and was increased after 3 days of recovery in air. Expression of FGF-R1 was not affected by exposure to 95% O2 or recovery in air. We hypothesized that the increase in bFGF after removal from 95% O2, acting through the FGF-R1, would be critical for compensatory growth. Intraperitoneal injection of soluble truncated FGF-R1 at the onset of the recovery phase arrested compensatory lung DNA synthesis and secondary septation seen in control animals after 3 days of recovery, confirming a role for FGF-R1 in this model of compensatory neonatal lung growth.     

Transcription-targeted gene therapy for androgen-independent prostate cancer

The Escherichia coli enzyme (purine nucleoside phosphorylase, PNP) gene is delivered directly into PC3 tumors by one injection of replication-deficient human type-5 adenovirus (Ad5). Expressed PNP converts the systemically administered prodrug, 6MPDR, to a toxic purine, 6MP, causing cell death. We sought to increase the specificity of recombinant Ad vectors by controlling PNP expression with the promoter region from the androgen-dependent, prostate-specific rat probasin (Pb) gene. To increase its activity, the promoter was combined with the SV40 enhancer (SVPb). Cell lines were transfected with plasmids containing both a reporter gene, under SVPb control, and a reference gene cassette to allow normalization of expression levels. Plasmids expressed approximately 20-fold more reporter in prostate cancer than in other cells, but surprisingly, the SVPb element was both androgen-independent and retained substantial prostate specificity. Killing by Ad5-SVPb-PNP vector of cell lines cultured with 6MPDR for 6 days was 5- to 10-fold greater in prostate cancer than in liver or lung cells. In vivo, a single intratumoral injection of Ad5-SVPb-PNP (4 x 10(8) pfu), followed by 6MPDR administration twice daily for 6 days, significantly suppressed the growth of human prostate tumors in nude mice and increased their survival compared to control animals. Thus, the androgen-independent, prostate-targeting Ad5 vector reduces human prostate cancer growth significantly in vitro and in vivo. This first example of an androgen-independent vector points the way toward treatment of emerging androgen-independent prostate cancer in conjunction with hormone ablation therapy at a time when the tumor burden is low.     

Fécondité féminine et activité physique intense et répétéeFemale fertility and intensive physical activity

Aims – To estimate the effects of intensive physical activity on female fertility.Current knowledge – Since twenty to thirty years ago, women have regularly participated in intense physical sports. The first Olympic Marathon for women took place at Los Angeles (United-States) in 1984 and many clinical studies concerning the incidence of menstrual disturbances among sportswomen, were concomitant of the dramatic increase in female participation in endurance sports, either as recreational or professional sportswomen. Most of these studies were focused on secondary amenorrhea. Later, etiological studies have shown that a range of disturbances, from an apparently normal menstrual cycle, irregular menstruation, oligomenorrhea to the complete blockage of the ovarian function were observed.Points of views and plans – It is very likely that the physiological process leading to menstrual troubles among sportswomen include disturbances of GnRH pulsatility at hypothalamic level. It has been shown that a session of training at an intensity greater than 60% during at least 40 min leads to the secretion of neuromediators able to interfere with GnRH pulsatility. Repetitiveness of daily sessions of training (i.e., more than five sessions a week) associated with marginal energy intake or strictly vegetarian food may contribute to disturb the hypothalamo-pituitary-ovarian axis in female athletes.     

Derivation of MPR and TRAMP models of prostate cancer and prostate cancer metastasis for evaluation of therapeutic strategies

Pre-clinical models of primary and metastatic prostate cancer are increasingly needed to evaluate efficacy of the new therapeutic strategies currently under investigation. The androgen-independent RM1 and androgen-dependent TR cell lines derived from transgenic mouse models of prostate cancer were examined in this regard. Following implantation in immune competent mice, the RM1 cell line was able to generate extremely fast growing s.c. and iprost tumors and metastatic lung lesions providing a time period of approximately 14-17 days from the time of tumor establishment to animal sacrifice to assess therapies. Implantation of TR cell lines resulted in more slowly growing s.c. and iprost tumors and metastatic lung lesions that exhibited highly variable incidence and growth. These models represent the best available means to evaluate therapeutics in primary and metastatic prostate cancer variants in an intact immune system.