Psychological stress in patients with anal fistula.

AIM: Psychological stress is known to affect the immunologic system and the inflammatory response. The aim of this study was to assess the presence of psychological stress, anxiety, and depression in patients with anal fistula. METHODS: Consecutive patients with anal fistula, hemorrhoids, and normal volunteers were studied prospectively. Stressful life events were recorded and subjects were asked to complete the state-trait anxiety inventory (STAI), a depression scale, and three different reactive graphic tests (RGT). RESULTS: Seventy-eight fistula patients, 73 patients with grade III-IV hemorrhoids, and 37 normal volunteers were enrolled. Of the fistula patients, 65 (83 %) reported one or more stressful events in the year prior to diagnosis, compared to 16 (22 %) of the hemorrhoid patients (P = 0.001). There were no significant differences in the percentage of subjects with abnormal trait anxiety (i.e., proneness for anxiety) and depression scores between fistula patients, hemorrhoid patients, and controls. Fistula patients had significantly higher (i.e., better) scores compared to hemorrhoid patients in two of three RGT and significantly lower (i.e., worse) scores in all three RGT compared to healthy volunteers. Of 37 patients followed up for a median of 28 months (range 19-41 months) after surgery, 8 (21.6 %) had persistent or recurrent sepsis. There was no significant difference in depression, STAI, and RGT scores between patients with sepsis and patients whose fistula healed. CONCLUSION: Our results suggest that an altered emotional state plays an important role in the pathogenesis of anal fistula and underline the importance of psychological screening in patients with anorectal disorders.

Psycho-echo-biofeedback: a novel treatment for anismus--results of a prospective controlled study.

BACKGROUND: Anismus or non-relaxing puborectalis muscle (PRM), detectable with anal/vaginal ultrasound (US), is a cause of obstructed defecation (OD) and may be treated with biofeedback (BFB). Many patients with anismus are anxious and/or depressed. The aim of this prospective study was to evaluate the outcome of the novel procedure psycho-echo-BFB in patients with anismus and psychological disorders. METHODS: Patients presenting at our unit with anismus and psychological disorders between January 2009 and December 2013, and not responding to conventional conservative treatment, were enrolled in the study. All underwent four sessions of psycho-echo-BFB, carried out by two psychologists and a coloproctologist, consisting of guided imagery, relaxation techniques and anal/vaginal US-assisted BFB. A validated score for OD was used, and PRM relaxation on straining measured before and after the treatment. PRM relaxation was also measured in a control group of 7 patients with normal bowel habits. RESULTS: Ten patients (8 females, median age 47 years, range 26-72 years) underwent psycho-echo-BFB. The OD score, evaluated prior to and at a median of 25 months (range 1-52 months) after the treatment, improved in 7 out of 10 patients, from 13.5 ± 1.2 to 9.6 ± 2.2 (mean ± standard error of the mean (SEM)), p = 0.06. At the end of the last session, PRM relaxed on straining in all cases, from 0 to 7.1 ± 1.1 mm, i.e., physiological values, not statistically different from those of controls (6.6 ± 1.5 mm). Two patients reported were cured, 3 improved and 5, all of whom had undergone prior anorectal surgery, unchanged. No side effects were reported. CONCLUSIONS: Psycho-echo-BFB is safe and inexpensive and allows all patients with anismus to relax PRM on straining. Previous anorectal surgery may be a negative predictor.

Abnormal glycosylation of hemopexin in arthritic rats can be blocked by bindarit.

Induction of arthritis in rats with Freund's complete adjuvant was accompanied by a distinctive alteration of concanavalin A (Con-A) reactivity in their serum proteins in which the concentrations of selected Con-A reactive proteins were significantly higher when compared to healthy rats. To assess if the observed increase in Con-A reactivity of specific serum proteins reflects an increase in carbohydrate moieties in these proteins in addition to an increase in their protein concentrations, a heme binding serum glycoprotein, hemopexin, also an acute phase reactant, was selected as a marker protein. Hemopexin was purified to apparent homogeneity from pools of serum samples derived from rats with yeast induced inflammation, a monospecific polyclonal antibody was prepared and was used for immunoblot analysis. It was noted that the concentration of hemopexin increased in rats with adjuvant induced arthritis; however, its concentration fell to normal levels after administration with a newly synthesized drug, bindarit, (2-[(1-benzyl-indazol-3-yl)methoxy]-2-methyl propionic acid, C19H20N2O3. Hemopexin was micropurified individually from healthy rats, adjuvant induced arthritic rats, and adjuvant arthritic rats treated with bindarit, cleaved with a Glu-C endopeptidase, Staphylococcus aureus protease V8, and the resultant peptide fragments resolved by SDS-PAGE and examined by silver staining, Coomassie blue staining, and lectin blots using Con-A. It was subsequently noted that hemopexin isolated from adjuvant induced arthritic rats showed a significant increase in Con-A reactivity in selected peptide fragments and that such an increase in glycosylation could be reversed to a pattern similar to healthy rats following treatment with bindarit.(ABSTRACT TRUNCATED AT 250 WORDS)

A new protein antidenaturant agent, bindarit, reduces secondary phase of adjuvant arthritis in rats.

Bindarit (or 2-[(1-benzyl-indazol-3-yl)methoxy]-2-methyl propionic acid) reduces heat induced denaturation of bovine and rat serum albumin in vitro (EC50 = 8.5 and 65 micrograms/ml, respectively) and inhibits heat induced serum albumin denaturation after in vivo (12.5-25-50 mg/kg po) administration in rats. To assess the relationship between protein denaturation and the development of chronic inflammatory diseases, the drug (0.5 or 0.12% medicated diet) was studied in comparison with indomethacin (1 mg/kg po daily) in rats injected with complete Freund's adjuvant. Bindarit appeared different from aspirin-like drugs, antiinflammatory steroids and immunosuppressants because it does not reduce primary inflammation of arthritic rats and was shown to be completely inactive on cyclo and lipooxygenase activity in vitro and on immune reactions of mice in vivo. Nevertheless, the drug strongly reduced the development of the secondary phase of adjuvant induced arthritis. The most significant effect of bindarit in this phase was a strong inhibition of serum albumin denaturation in arthritic rats. Assessment of both electrophoretic and quantitative changes suggests that the reduction of albumin during inflammation is due, at least in part, to a denaturation of native albumin, which loses its electrophoretic mobility. The involvement of protein denaturation in the production of new antigenic determinants, their pathogenic relevance in the development of adjuvant arthritis and the possibility that protein stabilization by bindarit could be the mechanism of action of the drug are discussed.

Effects of benzydamine eye drops on the rabbit's eye reaction to surgical, physical, and chemical stimuli.

The effects of benzydamine eye drops on the ocular reaction to different irritating stimuli in rabbits are reported. Benzydamine at the concentration of 0.1% reduces inflammatory tissue changes induced by AgNO3 burning of the cornea and inhibits the blood-aqueous barrier breakdown due to peripheral iridectomy or laser irradiation of the iris. Benzydamine reduces the aqueous PGE2 concentration to a similar extent as a 0.5% commercially available eye drop formulation of piroxicam. This result is in contrast with previous in vitro results demonstrating that benzydamine is devoid of any effects on PG synthesis. The possibility that PGE2 reduction is an indirect effect due to other biochemical activities of benzydamine is discussed. In the normal eye benzydamine manifests a local anaesthetic effect which is not accompanied by irritative changes in the anterior segment of the eye, changes in the intraocular pressure or pupillary size. It is suggested that in the clinical use of benzydamine eye drops the local anaesthetic activity may contribute to reducing both the neurogenic component of ocular inflammation and acute pain following injuries to the eye.

Review of pharmacological data on benzydamine.

Pharmacological results are reviewed supporting the use of benzydamine in so-called "primary inflammations" rather than in rheumatic diseases. In experimental studies, benzydamine shares with aspirin-like drugs their activity in acute inflammatory responses but not in Freund's adjuvant arthritis. The efficacy of benzydamine is mainly manifested against phenomena such as pain and oedema which depend on local mechanisms in the inflammatory focus. Other manifestations such as hyperthermia which are indicative of systemic functional involvement, are poorly affected by the drug. Benzydamine also lacks some of the typical side-effects of aspirin-like drugs which are thought to reflect their generalized activity. Finally topical application increases the analgesic and antiinflammatory activities of benzydamine much more than those of other antiinflammatory drugs. The data reported demonstrate that benzydamine specifically acts on the local mechanisms of inflammation. In order to explain this feature the chemical, pharmacokinetic and biochemical properties of benzydamine are discussed.

A comparative pharmacological study of trazodone, etoperidone and 1-(m-chlorophenyl)piperazine.

Since 1-(m-chlorophenyl)piperazine (mCPP) is a metabolite of trazodone (TRZ) and etoperidone (ETO), two atypical antidepressants, a pharmacological study was undertaken to establish the possible contribution of mCPP to the effects of the parent compounds. Behavioral effects of mCPP in rats consist in head shakes and other signs of serotoninergic stimulation; subtoxic doses also produce clonic convulsions and prostration. TRZ and ETO produce sedation and signs of alpha-adrenergic blockade; subtoxic doses produce tremors, clonic convulsions and prostration. Peripheral effects of norepinephrine (NE) and serotonin (5-HT) in rats are potentiated by mCPP and inhibited by TRZ and ETO. 5-hydroxytriptophan (5-HTP)-induced head twitches in mice are inhibited by TRZ and ETO and unaffected by mCPP. At similar doses mCPP, TRZ and ETO inhibit some nociceptive responses in rats and mice.

Pharmacological investigations on lonidamine.

The results of a broad pharmacological screening on 1-[(2,4-dichlorophenyl)-methyl] -1H-indazole-3-carboxylic acid ( lonidamine ) a new antitumour agent which also possesses antispermatogenic and embryotoxic effects, are reported. Lonidamine does not affect general behaviour and autonomic functions and is devoid of anticonvulsant, anti-reserpine, anti-apomorphine, anti-amphetamine, antitremor , antipyretic, antiinflammatory and analgesic effects. It also lacks those side effects which are considered characteristic of different antitumour agents, such as thymus and spleen atrophy, delay in skin wound healing and damage to the gastrointestinal mucosa. At doses 40 times higher than that of hydrochlorothiazide, lonidamine produces diuretic effects. The practical importance of these findings in the current therapeutic use of lonidamine appears to be limited. The most typical signs of acute intoxication produced by high doses of lonidamine are salivation, lacrimation, diarrhea, ataxia, muscle rigidity and prostration with superimposed convulsions.

Effects of lonidamine alone or combined with hyperthermia in some experimental cell and tumour systems.

Lonidamine or 1-[(2, 4-dichlorophenyl) methyl]-1H-indazole-3-carboxylic acid, studied in a battery of in vitro and in vivo tests currently used for the screening of anti-tumour agents affecting cell division, has been shown to have a narrow spectrum of anti-tumour activity. The significance of this finding is discussed in the light of previous investigations suggesting that lonidamine affects mitochondrial function and not cell replication. Hyperthermia has been shown to sensitize tumour cells to lonidamine. This observation indicates that in combination with hyperthermia lonidamine has some potential for the treatment of cancer; moreover, it suggests that hyperthermia might reproduce a metabolic condition occurring in some stages of the disease. The blood levels corresponding to the anti-tumour action of lonidamine in animals are in the range of those detected in patients treated with the drug.

Energy metabolism of normal and lonidamine-treated Sertoli cells of rats.

The effect of lonidamine on oxygen consumption, aerobic lactate production, and [U-14C]glucose metabolism of rat Sertoli cells was investigated. The results may be summarized as follows: (1) Sertoli cells show well-developed energy metabolism both in vitro and in vivo. (2) The rate of aerobic lactate production is markedly higher than in other cell types, either normal differentiated or neoplastic, such as Ehrlich ascites tumor cells. (3) Lonidamine does not affect respiration and aerobic glycolysis of Sertoli cells. This finding is consistent with previous data which demonstrated that the antispermatogenic effect can be mainly ascribed to an irreversible alteration of germ cell mitochondria induced by 1-substituted indazole-3-carboxylic acids of which lonidamine represents one of the most potent derivatives. (4) The functional impairment induced by lonidamine on rat Sertoli cells cannot be ascribed to an action on the energy metabolism even if, up to date, the biochemical target is still unclear.

Sertoli cells of adult rats in vitro. II. Effect of different steroid precursors on estradiol 17 beta-synthesis.

The estradiol 17 beta-synthesis by delta 4 pathway has been studied in homogenous cultures of Sertoli cells isolated from adult rat testes. The data reported clearly demonstrate that progesterone, androstenedione, testosterone and estrone induce an increase of the estradiol 17 beta-production.