Modulation of a subthreshold calcium current by the neuropeptide FMRFamide in Aplysia neuron R15

1. The effect of the endogenous neuropeptide FMRFamide (Phe-Met-Arg-Phe-amide) on the Aplysia bursting pacemaker neuron R15 was studied. Brief local applications of FMRFamide, both on R15 somata in situ, and on R15 somata that were isolated and maintained in primary cell culture, cause a hyperpolarization of the membrane potential and a suppression of spontaneous bursting or beating pacemaker activity. 2. Two-electrode voltage-clamp experiments revealed that FMRFamide decreases the amplitude of an inward current, which activates with depolarization starting at a membrane potential less depolarized than the threshold for action potentials. Previous studies have established that this subthreshold inward current is carried by calcium and is essential for the generation of bursting pacemaker activity in Aplysia neurons. The effect of FMRFamide on the subthreshold inward current of R15 is blocked by divalent cation calcium channel blockers, such as cobalt and manganese, and is unaffected by changing the external concentration of potassium or chloride ions, or addition of blockers of the calcium-activated potassium current, such as external tetraethylammonium or internal EGTA. 3. The subthreshold calcium current of R15 is also decreased by dopamine and by an unidentified synaptic neurotransmitter. These substances mimic and occlude the action of FMRFamide on the subthreshold calcium current, suggesting that all three transmitters converge to affect the same population of calcium channels in neuron R15. 4. The subthreshold calcium current is enhanced by neurotransmitters that elevate cyclic AMP in R15, including serotonin, and the Aplysia neuropeptide egg-laying hormone (ELH). Likewise, the effect of FMRFamide on the subthreshold calcium current is enhanced by serotonin, ELH, and a cyclic AMP analog, suggesting that FMRFamide and cyclic AMP have antagonistic actions on the same population of calcium channels in neuron R15. 5. We conclude that the suppression of spontaneous bursting or beating pacemaker activity in neuron R15 by FMRFamide is due to a decrease in the subthreshold calcium current. The subthreshold calcium current in R15 is a common target for modulation by many different transmitters, acting via several distinct molecular mechanisms.     

Significance of right ventricular filling for left ventricular enddiastolic pressure-volume relationship under acute hypoxia in the dog

Summary In 14 closed-chest dogs, the significance of right ventricular filling for left ventricular enddiastolic pressure-volume relationship was investigated under acute hypoxia by means of single plane cineventriculography and simultaneous intraventricular pressure recording.Both after 5 min asphyxia (respirator switched off) (n=5) and after 3 min hypoxia (ventilation with pure N₂) (n=9), there was a significant leftward shift (p<0.005) of the left ventricular enddiastolic pressure-volume curve as compared to the control curves under normoxia. To simulate the elevated filling of the right ventricle under acute hypoxia, rapid intraventricular infusion was applier under normoxic conditions to raise right ventricular enddiastolic pressure to the same values as that measured under hypoxia. The extent of the ensuing leftward shift of the left ventricular enddiastolic pressurevolume curve was on average 60% of the shift under hypoxia in both sets of experiments. Neither the slope of the relationship between volume stiffness and enddiastolic pressure, nor the relationship between tangent elastic modulus and left ventricular wall stress, was affected by hypoxia or asphyxia.Thus, the shift of the left ventricular enddiastolic pressure-volume curve in the early stage of hypoxia is predominantly due to the influence of increased right ventricular filling. Since the increased volume of the atria under acute hypoxia limits left ventricular distensibility additionally, the changes in left ventricular enddiastolic pressure-volume relationships, observed in the early stage of hypoxia are mainly, or even entircly, the result of interaction of the various heart compartments, and not a reflection of alterations in myocardial tissue elasticity.Preliminary results were presented at the symposium on Cardiac adaptation to hemodynamic overload, training and stress in Tübingen (1983)Supported by the Deutsche Forschungsgemeinschaft     

Evaluating the Impact of a Novel Peer-to-Peer Educational Modality on Knowledge and Attitudes About Perinatal Mood and Anxiety Disorders

Maternal and Child Health Journal - This study assessed whether the use of a peer-to-peer educational book, written and illustrated by women who experienced common mental disorders (CMDs) in the...     

The regional registry of gastro-intestinal cancer North Baden (2.2 million inhabitants)

Summary The advantages of a population-based registry are discussed. It is shown that a registry for gastro-intestinal cancer in a district with expert medical care based upon histo-pathological diagnosis, has the principal advantage that it limits the sites of material collection to a few effective contributors, thus providing highly accurate data. The disadvantage of collecting data by two separate steps should be tolerated. The geographic situation and the organization of the regional registry for gastro-intestinal cancer in North Baden are described and the incidences for these cancers for the years 1971–1975 are given for the population of 2.2 million.Supported by the DFG (SFB 136)     

Obesity and subcutaneous fat patterning in relation to survival of postmenopausal breast cancer patients participating in the DOM-project

Summary The effect of obesity and fat distribution on survival of breast cancer patients was studied prospectively in 241 women with a natural menopause who participated in a breast cancer screening project, the DOM-project in Utrecht, The Netherlands. Mean follow-up time was 9.1 years and endpoint of interest was death from breast cancer. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness.No significant differences in survival time between more obese (Quetelet's index 26 kg/m²) and leaner (Quetelet's index < 26 kg/m²) patients or between patients with central fat distribution and patients with peripheral fat distribution were observed. Analyses were stratified by axillary node status, estrogen receptor status, and way of detection (by first screening or afterwards). Results of the stratified analyses were suggestive of a modifying effect of these factors.The absence of an association between obesity and survival time might be explained by two counteracting mechanisms. On the one hand obesity might be related to impaired survival, due to a tumor growth promoting effect of extra-ovarian estrogens. On the other hand obesity might be related to improved survival in a screened population, because obese patients profit more from screening by earlier detection of tumors than leaner counterparts.     

The Burden of Obesity and Its Sequelae

Obesity [body mass index (BMI) ≥30 kg/m²] is common in many parts of the world, especially in the established market economies, formerly socialist economies of Europe and Latin America and the Caribbean, as well as the Middle Eastern Crescent. Worldwide, as many as 250 million people may be obese (7% of the adult population) and 2 to 3 times as many may be considered overweight (BMI 25 to 30 kg/m²). The prevalence of obesity seems to be increasing in most parts of the world, even in areas where obesity used to be rare.A waist circumference greater than 102cm in men and 88cm in women may be a more sensible classification than BMI to identify individuals who are at increased health risk because of obesity, but information on this point is still scarce.Increased fatness measured by a high BMI, large waist circumference or high waist/hip circumference ratio is associated with many chronic diseases as well as poor physical functioning. These all contribute to the costs associated with excess bodyweight. The economic costs of obesity can be broken down into 3 levels Direct costs: costs to the community related to the diversion of resources to the diagnosis and treatment of diseases directly related to obesity as well as the treatment of obesity itself. These costs have been estimated to account for 2 to 8% of total healthcare costs of various countries. Indirect (or societal) costs: these costs are related to the loss of productivity caused by absenteeism and premature death and disability pensions. There is a lack of good economic analysis in this area, although research from Sweden, Finland and The Netherlands has clearly shown that obesity is associated with increased sick leave and the need for disability pensions. Personal costs: obese individuals may earn less than their lean counterparts because of job discrimination (related to the stigma associated with obesity or because of diseases and disabilities caused by obesity). Many insurance companies (particularly life insurance) charge higher premiums with increasing degrees of overweight.In conclusion, there is much indirect information that obesity and overweight are important and growing public health concerns that contribute substantially to healthcare-related costs. Effective strategies for the prevention and management of obesity are needed.