Neuroendocrine control of body fluid metabolism

Mammals control the volume and osmolality of their body fluids from stimuli that arise from both the intracellular and extracellular fluid compartments. These stimuli are sensed by two kinds of receptors: osmoreceptor-Na+ receptors and volume or pressure receptors. This information is conveyed to specific areas of the central nervous system responsible for an integrated response, which depends on the integrity of the anteroventral region of the third ventricle, e.g., organum vasculosum of the lamina terminalis, median preoptic nucleus, and subfornical organ. The hypothalamo-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting vasopressin and oxytocin in response to osmotic and nonosmotic stimuli. Since the discovery of the atrial natriuretic peptide (ANP), a large number of publications have demonstrated that this peptide provides a potent defense mechanism against volume overload in mammals, including humans. ANP is mostly localized in the heart, but ANP and its receptor are also found in hypothalamic and brain stem areas involved in body fluid volume and blood pressure regulation. Blood volume expansion acts not only directly on the heart, by stretch of atrial myocytes to increase the release of ANP, but also on the brain ANPergic neurons through afferent inputs from baroreceptors. Angiotensin II also plays an important role in the regulation of body fluids, being a potent inducer of thirst and, in general, antagonizes the actions of ANP. This review emphasizes the role played by brain ANP and its interaction with neurohypophysial hormones in the control of body fluid homeostasis.     

Cerebral vasospasm and headache during sexual intercourse and masturbatory orgasms

BACKGROUND: The pathophysiology of the explosive type of headache associated with sexual activity is not completely understood. Five reported cases of patients with thunderclap headache, precipitated by sexual activity, in association with concomitant cerebral arterial narrowing, were found in the literature. METHODS: A 44-year-old woman with both coital and masturbatory headaches during orgasm associated with segmental reversible cerebral artery vasospasm was investigated. Cerebral anatomy and eventual spasm was documented by magnetic resonance imaging or digital angiography before, during, and after resolution of the orgasmic headache-vasospasm clinical manifestation. CONCLUSION: Findings of cerebral arterial narrowing, presented by some patients shortly after orgasmic headache attacks, support the hypothesis that segmental vasospasm may exert a role in the pathogenesis of this uncommon type of headache. The literature is reviewed, and possible mechanisms underlying the development of orgasmic headache are discussed.     

Chromosomal alterations in osteosarcoma cell lines revealed by comparative genomic hybridization and multicolor karyotyping

We characterized the chromosomal alterations in eight osteosarcoma cell lines (OST, HOS, U-2 OS, ZK-58, MG-63, SJSA-1, Saos-2, and MNNG) by comparative genomic hybridization (CGH); gains and losses of DNA sequences were defined as chromosomal regions with a fluorescence ratio, wherein all of the 95% confidence interval was above 1.25 and below 0.75, respectively. In four of 8 cell lines, multicolor karyotyping (MK) was added. CGH revealed the average number of aberrations per cell line was 20.8 (range: 10–31); the average numbers of gains and losses were 11.1 and 9.6, respectively. The frequent gains were identified on 1p21q24, 1q25q31, 7p21, 7q31, 8q23q24, and 14q21; frequent losses were at 18q21q22, 18q12, 19p, and 3p12p14. High-level gains were observed on 8q23q24, 5p, and 1p21p22. MK revealed the most common translocations in the four cell lines were t(8;9), t(1;3), t(3;5), t(1;13), t(2;6), t(3;17), t(1;15), t(10;20), and t(6;20). Chromosomes 1, 3, 8, 9, and 20 were most frequently involved in translocation events. The concordance rate of aberrations in CGH and translocations in MK was 76%. MK was useful to identify the chromosomal alterations and as a supplement to the CGH results in three of four chromosomes.     

Cellular signalling mechanisms in adaptation to ischemia-induced myocardial damage

Ischemic heart disease is the major cause of morbidity and mortality in the Western world. Ischemia-reperfusion injury may induce cardiomyocyte cell death by necrosis or apoptosis. The heart can be adapted to tolerate an ischemic event by preceding brief episodes of ischemia and reperfusion, called preconditioning. Preconditioning protects the heart when it is directed towards the heart itself either immediately before or several days before an induced ischemic event. Adaptation by preconditioning can even be achieved in other organs, and preconditioning one organ can protect another organ. Evidence suggests that preconditioning may be a naturally occurring adaptive process in vivo, and in humans unstable angina before acute myocardial infarction may represent the phenomenon. The mechanisms underlying the response are complex and intertwined, and probably differ between acute and delayed. as well as local or remote models. Based on animal experiments, it appears that preconditioning consists of a trigger phase with release of signal substance(s), a signal transduction phase where cascade reactions are induced, and an organ effector phase where mediator(s) ensure organ protection against necrosis and apoptosis. Understanding the underlying mechanisms of action is crucial to making therapeutic use of this powerful mode of myocardial protection.     

Selective and nonselective toxicity of TRAIL/Apo2L combined with chemotherapy in human bone tumour cells vs. normal human cells

Although TRAIL/Apo2L preferably induces apoptosis in tumour cells without toxicity in normal cells, many tumour cell types display TRAIL/Apo2L resistance. Whether TRAIL/Apo2L in combination with chemotherapy may overcome TRAIL/Apo2L resistance while maintaining tumour selectivity remains to be determined. Here, we report that while ActD, DOX and CDDP sensitised both OS and Ewing's tumour cell lines and normal cells (hOBs, synovial cells, fibroblasts) to TRAIL/Apo2L-induced apoptosis, the combination of etoposide (VP16) and TRAIL/Apo2L was selectively active on tumour cells without affecting normal cells. Sensitisation of OS cells and hOBs to TRAIL/Apo2L did not correlate with a compatible change in the gene expression profile of the receptors for TRAIL/Apo2L determined by quantitative real-time RT-PCR. Also, sensitisation of the TRAIL/Apo2L death pathway did not rely entirely on the chemotherapy-induced, caspase-dependent cytotoxicity. Further, chemotherapy did not cause a compatible change in expression levels of proteins such as Bcl-2, Bcl-x(L), Bax, cIAP2, XIAP and survivin. However, ActD, DOX and CDDP downregulated expression of cFLIP in OS cells as well as expression of p21 in normal hOBs. Interestingly, while VP16 also extinguished cFLIP in OS cells, which were sensitised for TRAIL/Apo2L by VP16, VP16 induced cFLIP and enhanced p21 levels in normal hOBs, which remained refractory to VP16 plus TRAIL/Apo2L. Together, our data reveal that TRAIL/Apo2L combined with certain chemotherapeutic drugs is toxic to bone tumour and normal human cells and suggest that cotreatment with TRAIL/Apo2L and VP16 provides an attractive approach for selective killing of tumour cells while leaving unaffected normal cells.     

Evaluation of the ability to make non-invasive estimation of muscle contractile properties on the basis of the muscle belly response

The histochemical and biomechanical relationships of limb muscles are examined in two groups of 15 men aged between 17 and 40 years. Seven muscles are chosen: biceps brachii, triceps brachii (TB), flexor digitorum superficialis, extensor digitorum, biceps femoris, tibialis anterior and gastrocnemius caput mediale (GCM). The aim of the preliminary study is to evaluate an alternative method based on a tensiomyographic (TMG) non-invasive measurement technique. The percentage of type I muscle fibres obtained with the histochemical method is 2.2 times higher for the slowest measured muscle (GCM) than for the fastest (TB). The contraction time of a muscle belly twitch response measured by TMG is 1.9 times higher for GCM than for TB. Statistical analysis of the data obtained by tensiomyographic and histochemical techniques shows a significant correlation between the contraction time of muscle response measured by TMG and the percentage of type I muscle fibres (correlation coefficient equals 0.93). Results of the study suggest using the TMG measuring technique as a basis for the estimation of the percentage of type I muscle fibres.     

Hyperventilation in panic disorder and social phobia

The aim of our study was to observe the induction of panic attacks by hyperventilation in a group of panic disorder and social phobia patients (DSM-IV). We randomly selected 26 panic disorder patients, 22 social phobics and 25 normal volunteers. They were drug-free for 1 week. Hyperventilation (30 breaths/min) was induced for 3 min. Anxiety scales were taken before and after the test. 61.5% (n = 16) of panic disorder patients, 22.7% (n = 5) of social phobics and 4.0% (n = 1) of control subjects had a panic attack after hyperventilating (p < 0.01, panic disorder vs. control; p < 0.05, panic disorder vs. social phobia; p = n.s., social phobia vs. control). Both anxiety disorder groups were more sensitive to hyperventilation than normal volunteers. The induction of panic attacks by voluntary hyperventilation may be an easy and useful test for validating the diagnosis in some specific panic disorder patients.     

LaminOss immediate-load implants: II. Clinical considerations of osteocompression

The sinusoidal thread design of the LaminOss (Impladent Ltd, Holliswood, NY) osteocompressive immediate-load implant is structured with minimal shear interface to function in horizontal planes and stimulate bone growth by the action of streaming potentials at the implant thread surface area. This implant design, when used with a unique surgical instrumentation technique, allows maximum bone to be molded and compacted circumferentially around the sinusoidal implant threads. The surgical technique of bone lamination around larger implant horizontal planes (or load-bearing areas) creates a stable foundation for placing this implant into immediate function. For the past 10 years this surgical procedure has provided patients with immediate function the day of implant placement. The clinical advantage of immediate implant loading enhances care acceptance and patient satisfaction.