Search PubMed⌕ Search

Biomedical subjects

G Stock

Publications and source records attributed to G Stock.

At least 19 recordsLinked to original sources

Collaboration between industry and academia--prospects for male fertility control.

Drug development within the pharmaceutical industry is probably the field with the highest level of regulations. Due to the complexity of the different components of drug development and drug surveillance the need for a sophisticated organization and infrastructure is obvious. In addition, there is a necessity for sufficient resources and long-term commitment as well as logistic and long-term knowledge management. In order to secure high professional standards at all levels of this highly complex value creating chain, the number of cooperative arrangements in the pharmaceutical industry are increasing. The identification of new targets in the drug finding process calls in particular for outside partners. At the same time the preparedness of non-industrial researchers to cooperate with industry has also increased significantly. The area of fertility control, especially male fertility control, provides an excellent example for this kind of cooperation between industrial and non-industrial partners. Here a cooperative network is described which probably meets practically all relevant criteria for both the non-industrial but also the industrial partner. Some principles for the management of such a cooperative network are discussed. We believe that this kind of network can serve as a model for similar networks in other fields.

Contraceptive Agents, Male↗

Relationship between rhythmic discharge patterns of neurons in the central nucleus of the amygdala, blood pressure fluctuations and cortical activity.

In the discharge sequences recorded from single neurons in the central nucleus of the amygdala of chronically instrumented awake cats, rhythmical patterns with period durations of 5-12 s were observed. At the same time blood pressure and the degree of synchronisation of the EEG showed similar period fluctuations with positive correlation to neuronal activity. It is proposed that the central amygdaloid nucleus uses rhythmic patterns to coordinate somatomotor and vegetative systems.

Amygdala↗

Development of new immunocontraceptives-industrial perspective.

Contraception has been practiced for thousands of years. Nevertheless, it took until the late 1950s and early 1960s before a major breakthrough in contraceptive technology was achieved by the introduction of oral hormonal contraceptives. However, we have not succeeded in the development of non-hormonal contraceptive that is comparable to the pill regarding its efficacy, safety, and acceptance. The immunological interference with the complex fertilization process is a very attractive target in this respect, whereby the zona pellucida, a non-cellular surrounding of all mammalian eggs, represents a potentially ideal target. Another interesting target are sperm: either for the development of a female contraceptive or for a male contraceptive, although the latter approach does not look very promising so far. In conclusion, given the enormous impact on mankind of a growing world population and given the very individual needs for contraceptive methods of different women in one and the same country and in different cultures we should make widely available a whole set of suitable, adjusted methods of fertility control and this includes the search for an effective method of male fertility control.

Contraception, Immunologic↗

Responses of single neurons in amygdala to interoceptive and exteroceptive stimuli in conscious cats.

The amygdala is critical for behavioral arousal and must therefore integrate a wide variety of inputs. We examined sensory inputs and the degree of convergence to single neurons in the amygdala in conscious freely moving cats. A pressor stimulus elicited responses, predominantly inhibitory, in one-half of the amygdalar neurons tested. Most neurons in the central and basal nuclei responded to carotid chemoreceptor activation typically with an excitation. Almost one-half of all amygdalar neurons tested, particularly in the central nucleus, received orthodromic input from the locus ceruleus, the substantia nigra, and/or the contralateral central nucleus of the amygdala. Exteroceptive sensory stimulation with optic, acoustic, tactile, and olfactory stimuli elicited responses in 33, 55, 39, and 59% of amygdalar neurons, respectively. Two-thirds of the neurons tested with more than one external stimulus modality responded in the same manner to the various stimuli (usually excitation), demonstrating a convergence of exteroceptive stimuli on single amygdalar neurons, particularly in the basal nucleus. Spontaneous and induced behavioral arousal elicited responses in 92 and 86% of neurons, respectively. Most neurons responded to multimodal exteroceptive stimuli and behavioral arousal in the same manner. We suggest that amygdalar inputs are highly varied and, in many cases, relatively nonspecific and that the amygdala integrates a large number of external and internal sensory modalities to regulate autonomic and behavioral responsiveness to various stimuli.

Amygdala↗

Orthostatic challenge during neuroleptic test dose: a possible predictor of short-term outcome.

Cardiovascular measurements were used as indicators of autonomic arousal during an orthostatic challenge test without medication and after a test dose of 150 mg perazine in 20 acute schizophrenic patients. Unmedicated schizophrenics showed elevated heart rates and elevated systolic and diastolic blood pressure in comparison to healthy volunteers. After a test dose of 150 mg perazine, responders (using BPRS outcome criteria after 23 days) showed a pronounced orthostatic heart rate reaction in comparison to nonresponders. Results are discussed in relation to arousal theories and central dopaminergic activity in schizophrenia.

Adult↗

Potassium channel activation in vascular smooth muscle.

1. Numerous compounds and changes in physical state functions shift the membrane potential of vascular smooth muscle to more negative values. The consequence is a vasodilatation because Ca2+ channels are closed. K+ channel opening frequently causes the hyperpolarization. 2. Acidification of the blood substitute solution and a fall in O2 partial pressure dilate arterial vessels. Acidosis is associated with a rise in K+ permeability and a simultaneous fall in Na+ permeability. Prostacyclin has a 20-30% share, and EDHF a 70-80% share, in hypoxic vasodilatation. Experiments with iloprost (PGI2 analogue) confirmed the K+ channel opening properties of this drug. A voltage-dependent K+ channel and a Ca(2+)-activated K+ channel, via the influence of cA-PK or cG-PK, are responsible for the hyperpolarization with iloprost and with oxygen deficiency. 3. Cicletanine and ajoene cause a concentration-dependent membrane hyperpolarization and are potent vasodilators. A cicletanine concentration, which is attained by the dosage given to patients, is sufficient to produce these effects. Ajoene exerts a hyperpolarizing and vasodilating influence even in a concentration which may occur in the extracellular space by the administration of a single garlic clove. 4. The stationary activation curve 'developed force vs. membrane potential' satisfactorily explains the effects of K+ channel openers. The tight electromechanical coupling expressed by this curve comprises a 50% vasorelaxation for a 2.5 mV hyperpolarization. In the linear part of the curve, the coupling ratio is 5.1 mV/g. 5. In the vascular smooth muscle, vasorelaxation can be evoked by membrane hyperpolarization which is linked to a simultaneous increase in K+ outward current and 42K+ efflux. In the case of substances whose influence is solely or partially receptor-mediated, cyclic nucleotides may be involved in vasorelaxation. Since cyclic nucleotides also hyperpolarize through an increase in K+ conductance, the resulting dilatation often cannot be divided into its single components. Therefore, it is sensible not to give the term "K+ channel opener" too fine a definition. The term should be applied to all substances and changes in physical states which predominantly increase the open probability of K+ channels finally via a conformational change in the cell membrane. For example, giving an acidic blood substitute solution (acidosis) is an intervention opening K+ channels. Which K+ channel and which single channel conductance is concerned in a particular case, and which 'mediator' may participate, become secondary questions.

Animals↗

Influence of different progestogens on blood pressure of non-anaesthetized male spontaneously hypertensive rats.

The aim of the study was to find out if synthetic progestins with significant antimineralocorticoid activity would have a beneficial effect on blood pressure. Male spontaneously hypertensive rats were treated daily for four weeks with different progestogens by subcutaneous injection. Arterial pressure of the conscious animals was measured at three-day intervals. Progestogens were dosed on the basis of their progestogenic activity, whereby the dosages corresponded to the 10-fold effective dose for inhibition of ovulation in rats. For comparison, spironolactone as well as progesterone itself were included in the study. After four weeks' treatment, plasma volume, extracellular fluid volume (ECFV) and the sodium and potassium concentrations in the plasma were measured. In control animals, there was a slight decrease in blood pressure over the four-week experimental period. Progesterone and spironolactone similarly influenced blood pressure. A new progestin with significant antialdosterone activity, dihydrospirorenone (code No. ZK 30.595), slightly but significantly decreased the ECFV, plasma sodium concentration and slightly but insignificantly decreased blood pressure as compared to vehicle-treated controls. Synthetic progestins lacking this antimineralocorticoid activity did not decrease blood pressure, but rather induced a slight increase in this animal model. The results clearly support the hypothesis that synthetic progestins, like endogenous progesterone, all of them with inherent antialdosterone activity, decrease the ECFV and so might have an impact on extracellular fluid hemostasis as well as blood pressure regulation.

Animals↗

Lovastatin in the treatment of hypercholesterolemia in CAPD.

The authors studied the effect of lovastatin on five hypercholesterolemic CAPD patients with high risk of atherosclerotic cardiovascular disease. Patients took lovastatin 20 mg once daily for a mean period of 4.5 months. Pre- and post-treatment values of LDL and VLDL totals (325 mg/dl and 292 mg/dl, respectively) and of HDL (42 mg/dl and 43 mg/dl, respectively) had no significant statistical difference. Lack of significance may be due to low number of patients and short trial time. The study did demonstrate that lovastatin is well tolerated in CAPD patients.

Adult↗

Sexual dimorphism of blood pressure: possible role of the renin-angiotensin system.

The prevalence of hypertension in men is higher than in women and the onset of this disease is earlier in male than in female subjects. In spontaneously hypertensive rats, males also have higher blood pressures than females. Evidence from epidemiological, physiological, molecular biological and morphological studies concerning this sexual dimorphism is reviewed. We demonstrate that the gonadal steroids testosterone and estrogen have important effects on the gene regulation of the renin-angiotensin system. This may in part contribute to the sexual dimorphism in blood pressure control. The direct effect of steroid hormones on genes related to hypertension provides a suitable paradigm to improve our understanding of molecular and cellular mechanisms of cardiovascular control.

Angiotensin II↗

Increased sensitivity to arousal in spontaneously hypertensive rats is partially dependent upon the amygdala.

This study was designed to determine the effects of behavioral arousal on baroreflex regulation of heart rate in stroke-prone SHR (spSHR) and to ascertain whether the integrity of the amygdala is necessary to mediate these effects. Heart rate responses to phenylephrine-induced increases in arterial pressure were used as an index of baroreflex sensitivity (BRS). spSHR had reduced BRS compared to WKR. Electrical stimulation of the amygdala suppressed BRS in conscious rats only at intensities that elicited behavioral arousal. When normalized for control bradycardiac responses, the spSHR demonstrated a greater suppression of BRS upon amygdalar stimulation than Wistar-Kyoto rats (WKR). Confrontation with a mouse, used to elicit behavioral arousal, attenuated BRS in both spSHR and WKR. Ablation of the central nucleus of the amygdala and adjacent tissue prevented confrontation-induced suppression of BRS both in WKR and spSHR. These data suggest that spSHR are more sensitive to suppression of BRS due to arousal elicited by stimulation of the amygdala. Furthermore, the amygdala is necessary for arousal-induced suppression of BRS in WKR and spSHR.

Amygdala↗