Tramadol inhibits the contractility of isolated human myometrium.

This study was conducted to determine whether the atypical opioid analgesic tramadol inhibits the contractility of isolated non-pregnant human myometrium. Ten strips of non-pregnant human myometrium stimulated with 55 mm potassium chloride (KCl) were treated with three concentrations (30, 100 and 300 µm) of tramadol to test for any inhibitory effect of tramadol. The effects of concurrent administration of the ß adrenoceptor antagonist propranolol (1 µm), the guanylyl cyclase and nitric oxide synthase inhibitor methylene blue (20 µm) and the opioid receptor antagonist naloxone (100 µm) with tramadol were also studied. Tramadol caused a concentration-dependent inhibition of KCl-induced myometrial contractility, which was statistically significant at all three concentrations of tramadol used. Propranolol significantly reversed the inhibitory effect of 100 µm tramadol on KCl-induced myometrial contractility but not that of 300 µm tramadol. Neither methylene blue nor naloxone reversed the inhibitory effect of tramadol on KCl-induced myometrial contractility. These results suggest that tramadol inhibits KCl-induced contractility of isolated human myometrium. They also suggest that tramadol relaxes the myometrium due to stimulation of ß1 adrenoceptors. However, the concentrations of tramadol required to relax the myometrium were high and likely to be attained at toxic doses, rather than therapeutic doses, of tramadol.

Role of epigenetics in pharmacotherapy, psychotherapy and nutritional management of mental disorders.

WHAT IS KNOWN AND OBJECTIVE: There is increasing evidence that epigenetics plays a major role in the pathogenesis of the idiopathic mental disorders. This article comments on the role of epigenetics in the pharmacotherapy, psychotherapy and nutritional management of these disorders. COMMENT: There are two classes of epigenetic drugs undergoing trials for treating the idiopathic mental disorders: DNA methyltransferase and histone deacetylase inhibitors. These drugs may fulfil the need for newer and more effective drugs for treating these disorders. Psychotherapy could exert its therapeutic effect in idiopathic mental disorders through epigenetic mechanisms. As nutrients like folic acid and vitamin B(12) can influence an individual's epigenome, especially early in life, abnormal intakes of such agents may be involved in the pathogenesis of the idiopathic mental disorders. Hence, adequate emphasis should be given to such factors in an individual's nutrition, especially early in life. Nutrients such as L-methylfolate and S-adenosylmethionine may also be useful in nutritional therapy of these disorders. WHAT IS NEW AND CONCLUSION: Epigenetics plays a key role in the pathogenesis of the idiopathic mental disorders. Due emphasis should be given to epigenetic mechanisms in the pharmacotherapy, psychotherapy and nutritional management of these disorders.

Tramadol inhibits the contractility of isolated caprine detrusor muscle.

The atypical opioid analgesic tramadol has been shown to provide beneficial clinical and urodynamic effects in patients with detrusor overactivity. The effect of tramadol on isolated detrusor muscle has not been studied. This study investigated the ability of tramadol to inhibit acetylcholine (ACh)-induced contractility of the isolated caprine (goat) detrusor muscle. The effect of three concentrations (30, 100 and 300 µm) of tramadol on 10 caprine detrusor strips contracted by the addition of 100, 200 or 400 µm ACh was studied. The sensitivity of tramadol-induced inhibition of ACh responses to treatment with the ß-adrenoceptor antagonist propranolol (1 µm) and the opioid receptor antagonist naloxone (100 µm) was also studied. Tramadol caused a concentration-dependent inhibition of ACh-induced detrusor contraction that was reversed by raising the concentration of ACh. Propranolol, but not naloxone, reversed the tramadol-induced inhibition of contractions to ACh in the detrusor. These results suggest that tramadol inhibits ACh-induced contractility of the isolated detrusor. They also suggest that tramadol does so by an indirect anticholinergic mechanism involving the stimulation of ß-adrenoceptors. Tramadol may be useful in managing clinical conditions requiring relaxation of the detrusor muscle. Although the concentrations of tramadol needed to relax the detrusor were relatively high, these could be clinically attained via intravesical administration.

Inhibition of isolated human myometrium contractility by minoxidil and reversal by glibenclamide.

This study investigated the ability of the antihypertensive drug minoxidil to inhibit potassium chloride (KCl)-induced contractility of the isolated human myometrium. Twelve strips of myometrium obtained from 12 patients who underwent hysterectomy were triggered to contract with 55 mM KCl before and after incubation with 3 concentrations (1, 3 and 10 microM) of minoxidil. The percent inhibition by minoxidil on the extent of contraction, and the area under the contractile curve of KCl-induced contraction of the myometrial strips was determined. Furthermore, the effect of 10 microM glibenclamide on the inhibition generated by 3 microM minoxidil on KCl-induced contractility was studied. It was found that minoxidil produced a concentration-dependent inhibition of KCl-induced contractility of the myometrium and that glibenclamide reversed this inhibitory effect. These results suggest that the inhibitory effect of minoxidil on isolated human myometrium contractility may prove useful in clinical conditions requiring relaxation of the myometrium.

Inhibitory effect of anticholinergics on the contraction of isolated caprine urinary bladder detrusor muscle.

This study investigated whether four anticholinergics which are not clinically used for relaxing the urinary bladder detrusor muscle inhibit the contraction of isolated caprine (goat) detrusor muscle: cyclopentolate (100 nm), homatropine (5 microm), ipratropium (500 nm) and valethamate (1 microm). The effects of these anticholinergics were compared with tolterodine (3 microm), an anticholinergic clinically used for relaxing the detrusor muscle. The inhibitory effect of each of these five anticholinergics was studied on six strips of caprine detrusor muscle made to contract with 100 mum acetylcholine (ACh) by determining the percent inhibition of height of contraction and the area under the contractile curve (AUC). It was found that all five anticholinergics inhibited the ACh-induced contraction of the caprine detrusor and that this inhibition was reversed by raising the concentration of ACh. Hence, these four anticholinergics, like tolterodine, may be useful in managing clinical conditions that require relaxation of the detrusor muscle.

Epigenetic biomarkers in psychiatric disorders.

The discovery of biomarkers in psychiatric disorders may help in the diagnosis, prevention and treatment of patients with these disorders. Here, I discuss the potential role of epigenetic biomarkers, that is, epigenetically altered genes and/or expression patterns of proteins or metabolites, in psychiatric disorders. Before epigenetic biomarkers can be clinically applied in these disorders, several issues need to be addressed. These include establishing a connection between biomarkers and the disease process; determining the predictive quality of the biomarkers; determining the effects of disease heterogeneity on the biomarkers; and identifying sample sources for the biomarkers that are easily accessible for testing.

The importance of cultural inheritance in psychiatric genetics.

Cultural inheritance, a genetic-based inheritance system transmitted by the brain, has previously been proposed to underlie normal behaviour and mental disorders. In cultural inheritance epigenetic mechanisms are involved in gene expression. This paper proposes that since there are marked epigenetic mechanisms involved in the expression of genes underlying primary (idiopathic) mental disorders, epimutations, rather than genetic mutations, underlie these disorders.

The importance of cultural inheritance.

Cultural inheritance refers to the storage and transmission of information by communication, imitation, teaching and learning. It is transmitted by the brain rather than by genes. However, it does have a genetic basis, the genes involved determining the structure of the brain. Cultural inheritance is considered to be the latest stage in the evolution of heredity. It is thought to have evolved by epigenetic mechanisms from genetic inheritance. This article proposes that cultural inheritance underlies normal behaviour and mental disorders.

Adverse reactions to radiocontrast media in an Indian population.

This study was conducted to determine the epidemiological characteristics and clinical presentation of adverse reactions to intravenous radiocontrast media (CM) in patients of Indian origin. 379 of 1798 patients who received either sodium iothalamate or sodium meglumine diatrizoate developed adverse reactions (i.e. 21.08% of patients). The incidence of mild, moderate and severe adverse reactions were 19.47%, 1.33% and 0.28%, respectively. One patient who developed a severe reaction expired. There were no differences in the incidence of adverse reactions according to gender (males 21.2%; females 20.8%; p = 0.907) or age (p = 0.876). The incidence of adverse reactions was significantly higher in patients with a history of previous reactions (45.5%) than in those with no history (20.9%; p = 0.046). The incidence of reactions was also significantly higher in patients with a history of predisposing factors such as bronchial asthma (69.2%) and diabetes mellitus (60.0%) than in those without such a history (20.6%; p = 0). The incidence of adverse reactions in patients who received premedication prior to CM administration because of a history of predisposing factors (21.4%) was not significantly different from that in patients who were not premedicated (21.2%; p = 0.974), a result probably due to inadequate premedication used in the study. The skin was the most commonly affected site of reaction.

Assessment of hyperactivation, acrosome reaction and motility characteristics of spermatozoa from semen of men of proven fertility and unexplained infertility.

Semen from men of proven fertility was compared with that of men with unexplained infertility to determine differences in spermatozoal functions such as hyperactivation and acrosome reaction and spermatozoal motility characteristics. The hyperactivated spermatozoa in both groups could be visualised on the monitor of the Computer Assisted Semen Analyser and they exhibited 'circling', 'thrashing', 'starspin' and 'helical' motility patterns and the mean hyperactivation rates were not significantly different. However, 20% of the men with unexplained infertility did not exhibit hyperactivation compared to only 4% in the fertile group. Furthermore, the semen from infertile men when evaluated for hyperactivation could be categorised into two groups with those having lower hyperactivation (< 10% or < 6% after 4 and 6 h of incubation respectively), forming the first group, and those having a higher hyperactivation rate constituting the second group. In the fertile men such distinct groups were not visible and the percentage hyperactivation ranged from 1 to 16%. No significant differences were observed in the rate of acrosome reaction of fertile and unexplained infertile men. The non-hyperactivated spermatozoa from unexplained infertile men showed a significant increase in path velocity (VAP), curvilinear velocity (VCL) and amplitude of lateral head displacement (ALH) and a decrease in linearity (LIN) and straightness (STR) compared to spermatozoa from fertile men. Furthermore, the hyperactivated spermatozoa from infertile men also showed an increase in progressive velocity (VSL) (only after 2 h of incubation) and LIN and decrease in ALH and beat cross frequency (BCF) compared to spermatozoa from fertile men. The results are discussed in the light of the importance of the above spermatozoal functions and spermatozoal parameters in fertilization.

Analysis of the motility parameters of in vitro hyperactivated hamster spermatozoa.

Golden hamster cauda epididymal spermatozoa under in vitro capacitating conditions exhibited time-dependent transformation of motility pattern, and the frequency of occurrence of a particular motility type was found to be dependent on the depth of the motility chamber used. The nonhyperactivated spermatozoa with planar motility were the most predominant at 0 hr irrespective of the depth of the motility chamber. But spermatozoa with the helical motility pattern were not detectable up to 6 hr when the Makler chamber was used, whereas in both the slide chamber and cannula, by 2 hr such spermatozoa constituted 90% of the total spermatozoa. However, by 6 hr the hyperactivated circular moving spermatozoa were the predominant type in all the chambers. Sperm motility chamber depths were also found to effect the motility parameter values of hamster spermatozoa, but this effect was also found to be dependent on the type of motility. Increase in chamber depth did not alter any of the motility parameter values of spermatozoa with hatchet type of motility and only increased the amplitude of lateral head displacement (ALH) in planar type. But in spermatozoa with the helical type of motility, an increase in chamber depth increased the progressive velocity (VSL), path velocity (VAP), curvilinear velocity (VCL), straightness (STR), linearity (LIN), and ALH. In spermatozoa with the circular type of motility, an increase in VSL, VAP, VCL, and ALH was also observed, but STR and LIN decreased. The hyperactivated spermatozoa could be distinguished from the nonhyperactivated spermatozoa because the former were swimming in circles, had low progressive velocity, decreased straightness and linearity of path, and also exhibited an increase in the amplitude of lateral head displacement compared to the nonhyperactivated spermatozoa. Further, the spermatozoa with helical motility could be differentiated from the nonhyperactivated, circular, and hatchet spermatozoa in that they had the highest VSL, VAP, VCL, and ALH. Spermatozoa with hatchet movement were slow and exhibited very low STR and LIN. Thus the motility parameters could be used to distinguish the nonhyperactivated and hyperactivated distal cauda epididymal spermatozoa.

A study on serum prolactin levels in schizophrenia: correlation with positive and negative symptoms.

Serum prolactin levels are determined in 116 schizophrenics and 120 control subjects. Values of prolactin levels of the patients are compared with the values of control of the same sex and age group. There is no significant difference between prolactin levels of controls and those with negative or positive symptoms of schizophrenia. Analysis, taking age into account, also does not show any significant difference between patients with positive or negative symptoms and controls. The relationship between nature of symptoms of schizophrenia and serum prolactin levels varies in different studies. The possible reasons for such variations are discussed.

A study of serum prolactin levels in schizophrenia: comparison of males and females.

1. Serum prolactin levels were measured in large cohorts of schizophrenic patients (67 males and 42 females) and normal subjects (78 males and 42 females). 2. There was no significant differences between the serum prolactin levels of patients and controls, except in the age group 15-29 years. There were no significant differences between the serum prolactin levels of males and females, either among the patients or the control subjects. 3. The rise in serum prolactin levels after the commencement of neuroleptic medication in the patients was greater in females than in males even though the female patients received neuroleptics at lower doses. 4. These data indicate that serum prolactin levels in unmedicated males and females are similar; however, the prolactin response to neuroleptic medication is greater in females than in males.