Effects of human sera and human serum albumin on mouse embryo culture

Human proteins normally used to supplement human in vitro fertilization—embryo transfer (IVF-ET) culture media were tested for their effects on mouse embryo development from the zygote stage. These proteins included follicular and luteal-phase maternal sera, fetal cord sera, and both human and bovine serum albumin. Our results revealed that both maternal and fetal cord sera did not permit mouse blastocyst formation. Furthermore, predialysis of the human maternal sera and removal of IgG by protein A column chromatography did not improve their support of mouse embryonic development to the blastocyst stage. Similar detrimental effects were observed with maternal sera from term-pregnant IVF-ET patients. Interestingly, these serum samples had supported the in vitro growth of the human zygotes which resulted in these patients' pregnancies. Only some batches of human serum albumin supported mouse blastocyst formation, whereas all sources of bovine serum albumin were effective in this regard. These results raise the question of the suitability of the mouse embryo culture system as a quality control for the testing of protein supplements for human IVF-ET.     

Pulse protein feeding pattern restores stimulation of muscle protein synthesis during the feeding period in old rats

Muscle loss during aging could be related to a lower sensitivity of muscle protein synthesis to feeding. To overcome this decrease without increasing protein intake, we proposed to modulate the daily protein feeding pattern. We showed that consuming 80% of dietary proteins at noon (pulse pattern) improved nitrogen balance in elderly women. The present study was undertaken in rats to determine which tissues are the targets of the pulse pattern and what mechanisms are involved. Male Sprague-Dawley 11- and 23-mo-old rats (n = 32 per age) were fed 4 isoproteic (18% protein) meals/d for 10 d. Then half of the rats at each age were switched to a 11/66/11/11% repartition of daily proteins (pulse pattern) for 21 d. On d 21, rats were injected with a flooding dose of L-(13)C-valine (50 atom% excess, 150 micromol/100 g body) and protein synthesis rates were measured in liver, small intestine and gastrocnemius muscle in either the postabsorptive or the fed state. Epitrochlearis muscle degradation rates and plasma amino acid concentrations were measured at the same times. The pulse pattern had the following effects: 1) it significantly increased liver protein synthesis response to feeding and postprandial plasma amino acid concentrations at both ages; 2) it restored a significant response to feeding of gastrocnemius muscle protein synthesis in old rats; and 3) it had no effect in small intestine or on muscle breakdown. Thus, using a pulse pattern could be useful in preventing the age-related loss of muscle by increasing feeding-induced stimulation of muscle protein synthesis.     

Interaction between the serotonergic system and HPA and HPT axes in patients with major depression: implications for pathogenesis of suicidal behavior

Disturbances in the serotonin (5-hydroxytryptamine, 5-HT) system constitute the neurobiological abnormality most consistently associated with suicide. This abnormality could be a marker of vulnerability predisposing individuals to auto-aggressive and impulsive behavior. However, other abnormalities, such as hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, have also been described in suicide victims. While inhibitory effects of adrenocorticosteroids on 5-HT(1A) receptor function have been shown in animals, HPA axis hyperactivity does not seem to be responsible for the reduced 5-HT activity found in depressed patients with a history of suicidal behavior. On the other hand, hypothalamic-pituitarythyroid (HPT) axis dysfunction, frequently observed in depression, may represent a compensatory response to reduced central 5-HT neurotransmission. Moreover, in depressed patients with a history of suicidal behavior, the absence of a functional link between HPT and dopamine activity at the hypothalamic level may be implicated in the pathophysiology of suicidal behavior. Future research is needed to determine why compensatory mechanisms are not efficient in patients with suicidal behavior.     

Neuropsychological deficit in early subcortical vascular dementia: comparison to Alzheimer's disease

To further clarify the cognitive syndrome in subcortical vascular dementia (VaD), we investigated 20 patients with early-stage VaD as compared with 30 patients with Alzheimer's disease (AD) and 22 normal controls using episodic memory, attention/executive function and language tests. The patient groups were closely matched in terms of age, education and severity of dementia. The VaD patients had a significantly better free recall, cued recall and recognition memory than AD patients, the recognition being within normal limits in VaD. In addition, VaD patients had a greater number of perseverative errors during the Modified Card Sorting test, while AD patients exhibited more perseverations of semantic fluency. The results of retrieval deficit syndrome and increased number of perseverations during tasks sensitive to frontal lobe function are in agreement with the studies emphasizing the importance of frontal dysfunction in subcortical VaD. These findings are relevant for the early diagnosis of VaD and might be useful in the differential diagnosis with AD.     

Rabies in a nine-year-old child: The myth of the bite

A nine-year-old boy died from rabies encephalitis caused by a rabies virus variant associated with insectivorous bats. The patient was most likely infected in the Laurentian Mountains of western Quebec, but neither the patient nor his parents remembered any direct contact with an animal. The diagnosis was made seven days after the start of symptoms. After examining the most recent cases of rabies in North America, it is obvious that rabies following bat exposure can occur without history of a documented bite. The present case report emphasizes that the general public and medical care providers need better information about the risks associated with exposure to bats.Key Words: Bat, Children, Encephalitis, Prophylaxis, RabiesRabies is a zoonosis responsible for more than 50,000 human deaths every year worldwide, as reported by the World Health Organization. In North America and Europe, human rabies has become a very rare disease, because of the systematic vaccination of domestic animals, massive vaccination campaigns of wild animals, efficacy of rabies postexposure prophylaxis (RPEP) and education programs (1,2). While knowledge about the risk of rabies associated with a bite from a terrestrial animal seems relatively adequate among the general public and medical care providers, a lack of information may exist regarding the risk of human rabies following contact with a bat. Between 1980 and 1996, 32 cases of human rabies were diagnosed in the United States, 17 of which occurred after a contact with an indigenous bat (of which only two patients had a definite bite), 14 cases after a dog bite and one after a skunk bite (3). In Canada, three of the four cases of human rabies that have occurred since 1970 followed exposure to bats, the last case dating to 1985 (4). Since September 2000, five cases of human rabies have been reported in the United States (5). One was consecutive to a dog bite contracted in Africa and four have been attributed to bats; in the latter cases, a definite history of a bite was noted in only one case. In 1996, the National Association of State Public Health Veterinarians of the United States stated that "since rabies is endemic in bats, bats should be excluded from houses and surrounding structures to prevent direct association with humans" (6). Possible measures to reduce the bat population to a critical threshold below which the virus might be unable to propagate or to induce immunity in the vector via vaccination seem physically, economically and ecologically impractical (7). The case that we report emphasizes that the bite or the scratch of a rabid bat can go unnoticed and may lead to the development of human rabies.     

The role of sexually transmitted infections in male circumcision effectiveness against HIV – insights from clinical trial simulation

Background  

A landmark randomised trial of male circumcision (MC) in Orange Farm, South Africa recently showed a large and significant reduction in risk of HIV infection, reporting MC effectiveness of 61% (95% CI: 34%–77%). Additionally, two further randomised trials of MC in Kisumu, Kenya and Rakai, Uganda were recently stopped early to report 53% and 48% effectiveness, respectively. Since MC may protect against both HIV and certain sexually transmitted infections (STI), which are themselves cofactors of HIV infection, an important question is the extent to which this estimated effectiveness against HIV is mediated by the protective effect of circumcision against STI. The answer lies in the trial data if the appropriate statistical analyses can be identified to estimate the separate efficacies against HIV and STI, which combine to determine overall effectiveness.     

Public and private pharmaceutical spending as determinants of health outcomes in Canada

Canadian per capita drug expenditures increased markedly in recent years and have become center stage in the debate on health care cost containment. To inform public policy, these costs must be compared with the benefits provided by these drugs. This paper measures the statistical relationship between drug spending in Canadian provinces and overall health outcomes. The analysis relies on more homogenous data and includes a more complete set of controls for confounding factors than previous studies. Results show a strong statistical relationship between drug spending and health outcomes, especially for infant mortality and life expectancy at 65. This relationship is almost always stronger for private drug spending than for public drug spending. The analysis further indicates that substantially better health outcomes are observed in provinces where higher drug spending occurs. Simulations show that if all provinces increased per capita drug spending to the levels observed in the two provinces with the highest spending level, an average of 584 fewer infant deaths per year and over 6 months of increased life expectancy at birth would result.     

Season of birth in valvular heart disease

This study demonstrates seasonal variations of birth dates in children with congenital valvular heart disease and in adults dying from valvular heart disease. The findings are based on the 1989-98 Swiss EUROCAT data, and on 1969-94 Swiss mortality records. Seasonality was tested with aggregated monthly data using Edwards' procedure. Both data sets showed excesses between December and March, consistent in different forms of valvular disease and in both sexes. Despite the decline of rheumatic heart disease, risk factors causing season of birth effects remain relevant for congenital anomalies.