Compound heterozygous SLC29A3 mutation causes H syndrome in a Moroccan patient: A case report.

H syndrome is an autosomal recessive syndrome, which affects the skin and some vital organs, it is caused by mutations in the SLC29A3 gene, encoding the human equilibrative nucleoside transporter hENT3. This report describes a patient with typical features of H syndrome. Based on the patient's clinical features, SLC29A3 was selected for molecular investigation. Through direct sequencing, a compound heterozygous alteration in the SLC29A3 gene was found. The c.243delA frameshift mutation leading to a premature termination, resulting in a truncated protein, and a splice site mutation c.300+1G>C predicted to cause a splicing error. This contribution extends the clinical variability of compound heterozygous SLC29A3 mutations resulting in an additional multisystemic manifestation of the clinical spectrum of SLC29A3 disorders.

Circadian variation and soccer performance: implications for training and match-play during Ramadan.

Ramadan results in a number of behavioural alterations in individuals when compared to their normal habits outside of this holy month. These changes in behaviour could impact upon the effectiveness of the activity of an elite athlete who has high daily activity levels and energy expenditures. Understanding the true impact of Ramadan on human physiology will also require an awareness of the key aspects of circadian rhythms. This article will present theoretical background content on circadian rhythms along with data on the potential influence of circadian variation on soccer performance. It will also attempt to provide an insight into the problems of partial sleep deprivation and travel for the elite player. The contents will suggest that there is a basis for the within-day variation in physiological and psychological function to impact soccer performance if games are played early in the day or very late at night. As competitive fixtures are uncommon at these times these influences may be more relevant to the timing and organisation of training sessions. It is also likely that a lack of sleep and excessive travel will provide conditions that are not conducive to optimal performance. This would indicate that teams should think carefully about their preparation strategies for important tournaments and games.

[The ethical implications of conserving biological samples]. / Les implications éthiques de la conservation des échantillons biologiques.

The conservation and use of biological samples become more and more frequent all around the world. Biobanks of human body substances (blood, urine, DNA, tissues, cells, etc.), and personal data associated with them are created. They have a double character as they are collections of both human biological samples and personal data. In some cases, the gametes, reproductive tissues, embryos, foetal tissue after abortion or even specimens of dead donors are collected and conserved. Although biobanks raise hopes in both the development of new therapies, new drugs and their integration into clinical medicine, they also point to concerns related to ethical questions such as: the principles of information, the consent of the persons concerned, the confidentiality about the personal data, and in some cases discrimination and stigmatisation. Other ethical aspects could raise gradually as research advance. Research being carried out on human sample requires informed free consent from the person who should be able to consent. The donor must be sufficiently informed about the process of research, the purpose, benefits and the risks involved in participating in this research. In the case of persons unable to give consent such minors or persons with mental disabilities, special measures are undertaken. Once the consent was given, the right of withdrawal has been consistently supported by the various declarations and regulations, but some oppose this right for a number of reasons particularly in the case of research on the samples without risk of physical exposure. In this case the notion of human body integrity is different than in research involving therapeutic or clinical intervention. In the case of withdrawal of consent, the samples should be destroyed, but the anonymous results arising from them and their analysis are not affected. What is the case for future uses? Should the researcher obtain again the consent from the donor for a secondary use of the samples? This is a matter of debate in the public and scientific communities. In Morocco, research activities on humans are undertaken in the absence of legal framework. Among the ethical issues, the most frequent in Morocco are related to the informed and explicit consent. Illiteracy, which concerns half of the population, and the economic vulnerability of the largest proportion of the patient make the informed and explicit consent questionable. In this paper we aimed to describe the use and conservation of human biological samples in Morocco and to determine the ethical questions raised in this context. An anonymous questionnaire was sent to biologists working in the different laboratories. The response rate was only 59.2%. The human biological samples are generally used for diagnosis and clinical follow-up. The storage period ranged from 3 months to 1 year, it does not exceed one year. The percentage of conservation of biological samples in the laboratory for one year is 67% and no basic criterion is maintained in the selection of samples. All laboratories obtained their samples directly from patients; no exchange or duplicate samples were undertaken between institutions. The analyses performed on the stored samples are biochemical and immunological. The genetic analyses accounted for only 35% of the total samples. The laboratories involved a researcy activity accounted for only 13.6%. Some of them answered they had not obtained in a systematic manner the consent of the persons concerned. These results indicated a lack of information and guidance on bioethics in Morocco.

Lipid profiles of judo athletes during Ramadan.

The effect of Ramadan intermittent fasting (RIF) was studied on a battery of blood lipid markers in 15 elite judo athletes during a period when they were maintaining their training load without competing. Nine-to-twelve hours postprandial serum lipid and lipoproteins were measured on five occasions: before, three times during Ramadan, and three weeks post-Ramadan. Dietary data were collected using a 24-hour recall method for three days before, during and after the Ramadan month. Mean energy intake (12.9 MJ/d) remained similar throughout the study as did the macronutrient constituents of the diet. Mean body mass was slightly reduced (2 %; p < 0.01) by the end of Ramadan due mainly to a 0.65 +/- 0.68 kg decrease in body fat (p < 0.05). The RIF produced significant changes in some of the blood lipid levels: both HDL-C and LDL-C increased by 0.12 (p < 0.01) and 0.20 mmol . l (-1) (p < 0.05), respectively. During Ramadan, mean non-esterified fatty acid (NEFA) levels decreased from 0.73 to 0.28 mmol . l (-1) (p < 0.01) during the first week, then increased (p < 0.05) to 1.22 mmol . l (-1) over the middle of Ramadan and recovered to pre-Ramadan concentrations for the end and the post-Ramadan periods. Apolipoprotein A1 (Apo-A1) levels were significantly elevated at the end (p < 0.01) and the post-Ramadan periods (p < 0.05). Three weeks after Ramadan, blood levels of glucose, NEFA, Apo-A1, and Apo-B did not return to the values observed before Ramadan. In conclusion, the present results show that the combination of the change in diet pattern during Ramadan, along with intense exercise training, induced a significant decrease in body mass associated with a reduction in body fat and changes in some of the serum lipids and lipoproteins. Nevertheless, all the measured serum parameters remained within normal levels for young and active individuals. The volunteers, in this study, were able to maintain a constant training load during RIF.

Diabetes and Ramadan: review of the literature.

During the month of Ramadan, Muslims fast every day from dawn to sunset. In the healthy subject, this fasting does not have any harmful consequences on health. However, it can induce several complications for patients with diabetes. The aim of this review twofold: first, it seeks to give some clues about methodological aspect of research during Ramadan and to show the impact of various diabetes monitoring and treatment, including biochemical and clinical parameters, diet and caloric intake, drug intake when fasting. Second, it intends to determine whether or not Ramadan fasting induces complications in patients with types 1 and 2 diabetes and ultimately to elaborate some advice as to the management of fasting patients. Several studies have shown that Ramadan fasting did not alter biochemical parameters in patients with type 2 diabetes. However, other studies have shown that there is either an increase or a decrease in biochemical parameters during Ramadan. Ramadan fasting would be acceptable for patients with well-balanced type 2 diabetes who are conscious of their disease and compliant with their diet and drug intake. If patients with type 1 diabetes wish to fast, it is necessary to advise them to undertake control of their glycaemia several times a day. Patients with type 1 diabetes who will fast during Ramadan may be better managed with fast absorption insulin.

Sleep during Ramadan intermittent fasting.

During the month of Ramadan intermittent fasting, Muslims eat exclusively between sunset and sunrise, which may affect nocturnal sleep. The effects of Ramadan on sleep and rectal temperature (Tre) were examined in eight healthy young male subjects who reported at the laboratory on four occasions: (i) baseline 15 days before Ramadan (BL); (ii) on the eleventh day of Ramadan (beginning of Ramadan, BR); (iii) on the twenty-fifth day of Ramadan (end of Ramadan, ER); and (iv) 2 weeks after Ramadan (AR). Although each session was preceded by an adaptation night, data from the first night were discarded. Polysomnography was taken on ambulatory 8-channel Oxford Medilog MR-9000 II recorders. Standard electroencephalogram (EEG), electro-oculogram (EOG) and electromyogram (EMG) recordings were scored visually with the PhiTools ERA. The main finding of the study was that during Ramadan sleep latency is increased and sleep architecture modified. Sleep period time and total sleep time decreased in BR and ER. The proportion of non-rapid eye movement (NREM) sleep increased during Ramadan and its structure changed, with an increase in stage 2 proportion and a decrease in slow wave sleep (SWS) duration. Rapid eye movement (REM) sleep duration and proportion decreased during Ramadan. These changes in sleep parameters were associated with a delay in the occurrence of the acrophase of Tre and an increase in nocturnal Tre during Ramadan. However, the 24-h mean value (mesor) of Tre did not vary. The nocturnal elevation of Tre was related to a 2-3-h delay in the acrophase of the circadian rhythm. The amplitude of the circadian rhythm of Tre was decreased during Ramadan. The effects of Ramadan fasting on nocturnal sleep, with an increase in sleep latency and a decrease in SWS and REM sleep, and changes in Tre, were attributed to the inversion of drinking and meal schedule, rather than to an altered energy intake which was preserved in this study.

Daytime alertness, mood, psychomotor performances, and oral temperature during Ramadan intermittent fasting.

During the month of Ramadan, Moslems abstain from drinking and eating daily between sunrise and sunset. This change of meals schedule is accompanied with changes in sleep habit, which may affect diurnal alertness. This study examined the effect of Ramadan intermittent fasting on the diurnal alertness and oral temperature in 10 healthy young subjects. The cognitive task battery including movement reaction time (MRT), critical flicker fusion (CFF) and visual analogue scale, was administered at 6 different times of the day: 09.00, 11.00, 13.00, 16.00, 20.00 and 23.00 h on the 6th, 15th, and 28th days of Ramadan. The baseline day was scheduled one week before Ramadan, and the recovery day 18 days after this month. Oral temperature was measured prior to each test session and at 00.00 h. During Ramadan oral temperature decreased at 09.00, 11.00, 13.00, 16.00 and 20.00 h and increased at 23.00 and 00.00 h. Subjective alertness decreased at 09.00 and 16.00 h and increased at 23.00 h. Mood decreased at 16.00 h. MRT was increased at the beginning of Ramadan (R6) and CFF was not changed. These results showed that daytime oral temperature, subjective alertness and mood were decreased during Ramadan intermittent fasting.

Food restriction alters the diurnal distribution of sleep in rats.

The purpose of the present study was to determine the effects of restricting food and water intake to the light period on sleep and brain temperature (Tbr). Sprague-Dawley male rats were anesthetized and provided with electrodes and thermistors for electroencephalographic (EEG) and Tbr recordings. Baseline recordings were performed after a 3-week recovery period. After baseline recordings, access to food and water was restricted (FWR) to the light period for 29 days. During FWR, the diurnal distribution of rapid-eye-movement sleep (REMS) and Tbr were reversed, while the distribution of non-REMS (NREMS) between the dark and light periods was attenuated. Daily food and water intake, body weight, and the diurnal distribution of EEG slow-wave activity within NREMS remained unchanged. In a separate study, sham-operated and pinealectomized rats were studied in a similar manner. The sleep responses of pinealectomized and sham-operated rats to FWR were similar. Further, FWR did not affect melatonin levels in the sham-operated rats, thereby suggesting that the pineal gland does not mediate the effects of FWR on sleep.

Epidemiological study: chronotype and daytime sleepiness before and during Ramadan.

Few epidemiological data have been reported on the relation between Ramadan fasting, life habits (meal frequency, sleep habits) and daytime sleepiness during Ramadan. This paper presents the results of a detailed study of the chronotype and daytime sleepiness before and during Ramadan. It was conducted on a sample of 264 subjects aged between 20 and 30 years. Results have revealed a significant decrease in the meal frequency during Ramadan compared with the control period. Before Ramadan, the majority of subjects woke up between 6 and 7 a.m. and went to sleep between 10 and 11 p.m. however, during Ramadan fasting, they woke up after 8 a.m. and preferred to go to sleep later (after midnight). Chronotype as evaluated by the Horne and Ostberg scale was changed significantly during Ramadan: an increase of the evening type and a decrease in the morning type of subjects was observed. Daytime sleepiness as evaluated by the Epworth Sleepiness Scale was significantly increased.

Distribution of prolactin receptors in the rat forebrain. Immunohistochemical study.

The distribution of prolactin receptors (PRL-R) in the rat brain was investigated for the first time with the immunohistochemical technique using monoclonal antibodies raised against PRL-R purified from rat liver. Granular immunostaining was observed in neurons and along their dendritic processes and fibers. PRL-R like immunoreactive neurons were found in a number of brain areas. There was a very dense labelling in the cerebral cortex (pyramidal cell layer), septal nuclei, amygdaloid complex as well as in the hypothalamus (suprachiasmatic, supraoptic, paraventricular and dorsomedial nuclei). A dense staining was seen in the substantia nigra, habenula and in the paraventricular thalamic nucleus. Immunostaining was also found in the choroid plexus and in the subcommissural organ. Comparison between the present distribution and that of PRL-like immunoreactivity indicates that the density of PRL-R generally corresponds to that of the fibers. However, in some regions densely stained by PRL-R antibody, there are very few PRL-immunoreactive fibers. These results are suggestive of different modes of action of PRL in the brain.

Prolactin and rapid eye movement sleep regulation.

During the past few years data have accumulated suggesting the involvement of prolactin (PRL) in rapid eye movement sleep (REMS) regulation. Pituitary PRL secretion seems to be, at least in part, sleep-dependent. PRL is also found in the central nervous system. PRL-containing neurons in the hypothalamus project to various structures in the brain. Systemic injection of PRL promotes REMS in rats, cats and rabbits. Intracerebroventricular injection of PRL enhances REMS in rats. Stimulation of endogenous PRL secretion by vasoactive intestinal peptide (VIP) also promotes REMS. Immunoneutralization of blood-borne PRL slightly reduces REMS. Various observations (hypoprolactinemic and hyperprolactinemic rats) indicate that PRL may act on REMS via modulating the diurnal rhythms of REMS. It is likely that hypothalamic PRL is more important for sleep regulation than circulating PRL. Hypothalamic PRL is likely involved in the mediation of the REMS-promoting activity of VIP. We conclude that PRL has a role in REMS regulation.

Cytokines in sleep regulation.

The central thesis of this essay is that the cytokine network in brain is a key element in the humoral regulation of sleep responses to infection and in the physiological regulation of sleep. We hypothesize that many cytokines, their cellular receptors, soluble receptors, and endogenous antagonists are involved in physiological sleep regulation. The expressions of some cytokines are greatly amplified by microbial challenge. This excess cytokine production during infection induces sleep responses. The excessive sleep and wakefulness that occur at different times during the course of the infectious process results from dynamic changes in various cytokines that occur during the host's response to infectious challenge. Removal of any one somnogenic cytokine inhibits normal sleep, alters the cytokine network by changing the cytokine mix, but does not completely disrupt sleep due to the redundant nature of the cytokine network. The cytokine network operates in a paracrine/autocrine fashion and is responsive to neuronal use. Finally, cytokines elicit their somnogenic actions via endocrine and neurotransmitter systems as well as having direct effects neurons and glia. Evidence in support of these postulates is reviewed in this essay.

Hypothalamic injection of prolactin or its antibody alters the rat sleep-wake cycle.

Several studies have suggested an interaction between prolactin and the sleep-wake cycle. In this study ovine prolactin (oPRL) and anti-prolactin antibody were microinjected into the rat dorsolateral hypothalamus, which contains prolactin-like immunoreactive neurons. Results indicate that during the light period, prolactin injection induced an increase in paradoxical sleep duration, whereas it caused a decrease when injected during the dark period. Anti-prolactin antibody injection during the dark period also decreased paradoxical sleep duration. There was no effect of oPRL or antibody on slow wave sleep duration irrespective of injection time. These results suggest that prolactin injection may have an inhibitory effect on hypothalamic prolactin neurons.

Anatomical distribution of prolactin-like immunoreactivity in the rat brain.

The present study examines prolactin PRL-like immunoreactivity (PRL-LIR) in the rat central nervous system and describes the distribution of labeled perikarya and fibers using a specific antiserum to ovine PRL. This antiserum does not cross-react with molecules of the pro-opiomelanocortin (POMC) family and recognizes rat PRL. PRL-LIR cell bodies are found exclusively in the lateral hypothalamic area surrounding the fornix, especially dorsolateral to it. No labeled cells are detectable in any other part of the brain, including the arcuate nucleus. Labeled fibers are dispersed in almost all parts of the brain. Dense plexuses are observed in the hypothalamus, midline thalamus nuclei, bed nucleus of stria terminalis, raphe dorsalis, and locus coeruleus. There is no apparent decrease in the number of PRL-LIR cell bodies and fibers in hypoprolactinemic mutant rats or after hypophysectomy, suggesting that central PRL is synthesized in such hypothalamic neurons. Comparison of PRL and alpha-melanocyte-stimulating hormone immunostainings provides evidence that the PRL network is independent of those of POMC and melanin-concentrating hormone. The present results support the hypothesis of two independent PRL systems: one peripheral (pituitary gland) and the other cerebral. Concerning the functional role of brain PRL, its widespread projections suggest that PRL is involved in multiple regulations. The presence of PRL-LIR in brain areas involved in sleep-wake control is a strong argument for its role in such a regulation.

Effect of prolactin on the sleep-wake cycle in the rat.

The purpose of this study was to examine the effects of prolactin on the sleep-wake cycle. Ovine prolactin was injected subcutaneous at a dose of 10 micrograms/animal or intra-cerebro-ventricularly at doses of 100, 10 and 1 ng/animal. The subcutaneous injections were given during either the diurnal or nocturnal period. Results indicate that oPRL decreases paradoxical sleep duration when injected during the dark period and increases it when injected during the light period. The i.c.v. injections were given only during the dark period and the effects were similar to those obtained with the s.c. injections. There was no effect on slow-wave sleep duration irrespective of injection time or injection site.