Psychometric properties and observational data for COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) for post-COVID-19 syndrome.

BACKGROUND: The recently developed modified COVID-19 (coronavirus of 2019) Yorkshire Rehabilitation Scale (C19-YRSm) captures comprehensive biopsychosocial components of WHO's International Classification of Functioning, Disability, and Health related to the Long Covid or post-COVID syndrome. The scale response categories on C19-YRSm were done post hoc on data collected from the original version of C19-YRS. AIM: To evaluate the C19-YRSm scale using reliability and validity measures. DESIGN: Prospective, observational study. METHODS: The study includes 369 patients (clinical group) and 426 subjects of the general population (control group) and captures their post-COVID-19 symptoms. In addition, the reliability of C19-YRSm was estimated by Cronbach's alpha coefficients of internal consistency and inter-item correlations for subscales ('Symptom severity, Functional disability, and Other symptoms'). Convergent validity was established using correlations between C19-YRSm and Fatigue Severity Scale (FSS). The incremental validity of C19-YRSm was measured by introducing a hierarchical regression model using the C19-YRSm 'Overall health' subscale and FSS as criterion variables. RESULTS: C19-YRSm subscales have excellent internal consistencies (Cronbach's α value 0.81-0.96) and acceptable inter-item correlations (r value 0.23-0.79). Hereafter, the convergent validity of the C19-YRSm is good due to significant correlations between C19-YRSm subscales and FSS and C19-YRSm subscales. Finally, the hierarchical regression analysis supported consistent evidence for the incremental validity of the C19-YRSm subscales. CONCLUSION: C19-YRSm is a reliable and valid self-assessment scale for the assessment of post-COVID-19 syndrome.

Opioidergic mechanisms are not involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in particular the role of opioid receptors, have not been established precisely. The systemic effects of naloxone, an opioid receptor antagonist, on the antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the model of inflammatory hyperalgesia induced by the intraplantar (i.pl.) administration of concanavaline A (Con A, 0.8 mg/paw) into the rat hind paw. Naloxone (3 mg/kg; i.p.) did not alter the antihyperalgesic effects of either carbamazepine or oxcarbazepine. These results indicate that the opioid system of pain modulation does not play a significant role in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

Role of alpha2-adrenoceptors in the local peripheral antinociception by carbamazepine in a rat model of inflammatory mechanical hyperalgesia.

The anticonvulsant carbamazepine was recently shown to possess local peripheral antinociceptive properties. In this study, we investigated whether alpha2-adrenergic receptors are involved in the local peripheral antihyperalgesic effects of carbamazepine and determined the type of interaction between carbamazepine and clonidine, an alpha2-adrenoceptor agonist. Intraplantar (i.pl.) coadministration of either carbamazepine (100-1000 nmol/paw) or clonidine (1.9-3.7 nmol/paw) with the proinflammatory compound concanavalin A (Con A; 0.8 mg/paw) caused a significant dose- and time-dependent reduction of the difference between the forces exerted by a rat's hind paws in a modified paw-pressure test. The coadministration of 260 and 520 nmol/paw (i.pl.) yohimbine, an alpha2-adrenoceptor antagonist, with carbamazepine, significantly depressed the local antihyperalgesic effect in a dose- and time-dependent manner whereas yohimbine by itself did not have any effect. The administration of a mixture of carbamazepine and clonidine at fixed dose fractions (1/4, 1/2 and 3/4) of ED50 caused a significant and dose-dependent reduction of Con A-induced hyperalgesia. Isobolographic analysis revealed an additive interaction. These results suggest that alpha2-adrenoceptors play a role in the local peripheral antihyperalgesic effects of carbamazepine and that local peripheral coadministration of carbamazepine with clonidine results in an additive antihyperalgesic effect.

Peripheral anti-hyperalgesia by oxcarbazepine: involvement of adenosine A1 receptors.

In this study we determined whether oxcarbazepine (OXC) could produce local peripheral antinociceptive effects in a rat model of inflammatory hyperalgesia, and whether adenosine receptors were involved. When coadministered with the pro-inflammatory compound concanavalin A, OXC (1000-3000 nmol/paw) caused a significant dose- and time-dependent anti-hyperalgesia. Caffeine (1000-1500 nmol/paw), a nonselective adenosine receptor antagonist, as well as 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (10-30 nmol/paw), a selective A1 receptor antagonist, coadministered with OXC, significantly depressed its anti-hyperalgesic effect. Drugs injected into the contralateral hind paw did not produce significant effects. These results indicate that OXC produces local peripheral anti-hyperalgesic effects, which is mediated via peripheral A1 receptors.

Nitric oxide (NO) and convulsions induced by pentylenetetrazol.

Data about the role of nitric oxide (NO) in epileptogenesis are contradictory. It is found to exert both proconvulsant and anticonvulsant effects. In an attempt to elucidate the role of NO in seizures, male Wistar rats were treated intraperitoneally by pentylenetetrazol (PTZ) (60, 80, and 100 mg/kg) and by a nitric oxide synthase antagonist, N-omega-nitro-L-arginine-methyl-ester (L-NAME) (10, 40, and 70 mg/kg), applied before PTZ. The time to onset and incidence of forelimb dystonia (FLD), generalized clonic convulsions (GCC), clonic-tonic convulsions (CTC), and mortality were recorded. The most successful convulsive response and mortality prevention were found in PTZ (80 mg/kg)-treated groups, where L-NAME (70 mg/kg) decreased the incidence by 29, 50, 67 (p = 0.052), and 50%, respectively, and significantly prolonged the time to onset, except that for mortality. Unexpectedly, L-NAME (40 mg/kg) increased incidence of GCC and mortality by 16%, similar to L-NAME (10 mg/kg) in PTZ (60 mg/kg)-treated groups, where GCC, CTC, and mortality increased by 14, 14, and 28%, respectively. Convulsive latency was prolonged in some PTZ (100 mg/kg) + L-NAME (40 and 70 mg/kg)-treated groups. In the experimental model and protocol used, it is concluded that (1) the effects of NO are L-NAME- and PTZ-dose dependent; (2) clonic-tonic convulsions are more strongly influenced by NO than limbic, probably because of PTZ limbic structure overstimulation; (3) L-NAME decreases the incidence of CTC and prolongs FLD, GCC, and CTC times to onset, indicating that NO acts as a proconvulsant; and (3) increased GCC, CTC, and mortality that suggests an anticonvulsant effect of NO needs further investigation.

The treatment of delayed polyneuropathy induced by diisopropylfluorophosphate in hens.

This study was undertaken to examine the influence of atropine, oximes and benzodiazepine on organophosphate-induced delayed polyneuropathy (OPIDP) in hens, which were poisoned with diisopropylfluorophosphate (DFP). The birds were treated with a standard neuropathic dose of DFP (1.1 mg/kg, s.c.), which produced typical signs of OPIDP. The development of OPIDP was observed within the followings 22 days. All drugs were given subcutaneously (s.c.), intramuscularly (i.m.) or intraperitoneally (i.p.), 20 min before the poison. The results obtained have shown that atropine (20 mg/kg, i.p.) only in combination with oxime TMB-4 (15 mg/kg, i.m.) produced significant improvement of OPIDP symptoms in comparison with positive control. Clinical signs and symptoms of OPIDP in the group which was treated with atropine (20 mg/kg, i.p.), TMB-4 (15 mg/kg, i.m.) and midazolam (2.5 mg/kg, i.m.) were more improved than that in the presence of a combination of atropine and TMB-4. The results of these experiments have shown that it is possible to prevent the development of DFP-induced OPIDP in hens by treatment with atropine and TMB-4 or atropine, TMB-4 and midazolam when given before DFP.

[Analgesic efficacy of Famalgin and Imigran in patients with acute migraine attacks]. / Ispitivanje analgetske efikasnosti Famalgin-a i Imigran-a kod bolesnika sa akutnim migrenskim atacima.

Migraine is a syndrome clinically manifested in attacks which dominant symptom is unilateral, rarely generalized, recurrent headache that can last for hours, and occasionally, days. According to different sources, it is considered that about 10-15% of world population suffers from some type of this syndrome. Migraine is most frequently clinically revealed in the age of 30-40, therefore in the most productive period with significant share in treatment costs and a great influence to the working ability of those patients. The aim of this trial was to determine analgesic efficacy of Imigran (sumatriptan) and Famalgin in the treatment of acute attacks of migraine headache. Trial results revealed significant analgesic efficacy of both preparations without significant differences in analgesic effect, with significantly better tolerability of Famalgin. It was concluded that both preparations were efficacious drugs for the treatment of headache as the most prominent clinical symptom of migraine, with significantly rarer and less pronounced adverse effects of Famalgin.

[Comparative study of the analgesic effect of Dikalm and Saridon in headaches of various causes]. / Uporedno ispitivanje analgetskog efekta Dikalma i Saridona u slucaju glavobolja razlicitog porekla.

Headache, as a syndrome, represents large health and wider socio-economic problem in every community for its massive occurrence and frequent absence of therapeutic response to the administered analgesics. That is why the finding, and later production of the drug that would satisfy the criteria of analgesic, efficacious in the treatment of headache, without the entering in etiology of syndrome are presented as the imperative. In connection with that was set the aim of the investigation: to investigate comparative analgesic efficacity of new preparation--Dikalm compared to analgesic that was for a long time present in our pharmaceutic market--Saridon tablets in the patients with different neurologic diseases, where headache represents the leading symptom of their difficulties. The investigation included 30 patients--10 patients were cross-examined with the use of both preparations in the treatment of headache episodes that appeared in separate time interval, and 20 patients received one another preparation. The headache intensity, residual headache, adverse effects and the need for repeating were graded by original standardized scales. The results of investigation revealed significantly better analgesic effect of therapeutic combination contained in Dikalm preparation, as for persistent, residual headache, as for the need of repeating the analgesics administration, what was specially pronounced in the group that cross-received both preparations, or in the whole group compared to the therapeutic combination contained in Saridon tablets. It was concluded that Dikalm represented the drug with efficacious analgesic and with minimal adverse effects.

[Adverse effects and toxicity of beta blockers]. / Nezeljeni efekti i toksicnost beta blokatora.

The adverse effects and interactions as well as clinical manifestations and treatment of beta blocker overdosage are reviewed. The most common adverse effects of these drugs arise from their pharmacological action and can be predicted and avoided. The serious unexpected adverse effects, like the so-called "practolol syndrome", are rare and do not occur in asso- ciation with currently available beta blockers. Drug interactions with beta blockers are not very common and have only minor clinical significance. Beta blockers have an extremly high benefit/risk ratio. Most patients who take an overdose of beta blockers are successfully treated.

HI-6 in man: efficacy of the oxime in poisoning by organophosphorus insecticides.

The efficacy of the oxime HI-6 was studied as a treatment for organophosphorus poisoning. HI-6 was given four times daily as a single intramuscular injection of 500 mg accompanied by atropine and diazepam therapy. Oxime treatment was started on admission and continued for a minimum of 48 h and a maximum of 7 d. HI-6 rapidly reactivated human blood acetylcholinesterase inhibited by dimethoxy organophosphorus compounds, while the dimethoxy-inhibited enzyme was mainly resistant to the treatment by HI-6. Although both HI-6 and pralidoxime chloride reactivated the red blood cell cholinesterase in quinalphos-poisoned subjects, the return of enzyme activities was more rapid following the use of HI-6. The general improvement of poisoned patients, which was sometimes more rapid than the rise of acetylcholinesterase activity, pointed to direct pharmacological effects of HI-6. No undesirable side-effects were noted in patients when HI-6 plasma concentrations were maintained at levels far above the 'therapeutic' concentration for up to 7 d.

[Effect of nitrendipine on isolated uterus and other smooth muscles of the rat]. / Effet de la nitrendipine sur l'utérus isolé et autres muscles lisses du rat.

Increasing concentrations of nitrendipine were found to inhibit various types of muscular activation (electrical stimulation, acetylcholine, oxytocin, potassium chloride), as well as the spontaneous rhythmic activity of the isolated rat uterus. The degree of the inhibitory effect of nitrendipine depends on the type of activation. Nitrendipine showed an exceptionally high efficacy in inhibiting contractions induced by electrical stimulation and of spontaneous rhythmic activity. For inhibition of these contractions even osmolar concentrations of nitrendipine were sufficient. The relaxant effect of nitrendipine depended on the concentration of extracellular calcium and the time of incubation of nitrendipine in the bathing medium. Nitrendipine showed high selectivity for the uterine smooth muscle because in a very high concentrations is exerted an insignificant relaxation of the other isolated smooth muscles (oesophagus, urinary bladder). Our experiments indicate that nitrendipine might have a role in therapy of premature delivery and abortion because of its great selectivity for the uterine smooth muscle. Addition of calcium into the medium restores completely all types of muscular activation after the inhibitory action of nitrendipine except its depressive action on the phasic component of oxytocin-induced contractions. These findings that individual types of activation, after inhibitory action of nitrendipine, are reestablished in various degrees by the addition of calcium into the medium, are also an additional confirmation about the existence of various types of calcium channels.

Soman intoxication-induced changes in serum acute phase protein levels, corticosterone concentration and immunosuppressive potency of the serum.

We have studied the effect of soman intoxication on serum acute phase reactants (APR) levels, and the relationship of the APR and corticosterone concentrations and the immunosuppressive activity of the serum. One day after the injection of 1.8 LD50 soman the concentrations of alpha 2-macroglobulin (alpha 2-MG) and alpha 1-acid glycoprotein (AGP) in the serum of antidote protected rats increased 4- and 7-fold, respectively, whereas those of hemopexin (Hx), haptoglobin (Hp) and cysteine protease inhibitor (CPI) were two to three times higher than in the controls. A similar magnitude of increase of serum acute phase reactants levels was observed when 0.3 LD50 soman was administered at 24-h intervals over the 5-day period. The relationship of changes in the APR concentration, corticosterone level and immunosuppressive activity of the serum was also comparable to that observed in the acute phase response to tissue injury.

Effect of soman intoxication on the organization of rat brain ribosomes and the translational activity of mRNA in a cell-free system.

The effect of soman on rat brain ribosomes organization and translational activity of mRNA in cell-free system was studied in rats exposed to 1.3 LD50 soman (120 micrograms/kg body weight) and in rats repeatedly injected with 0.4 LD50 soman (35 micrograms/kg). Fifteen minutes after the injection of 1.3 LD50 soman the heavy polyribosomal fraction from rat brain was found to be enriched and translational activity of mRNA was enhanced. In rats administered five injections of 0.4 LD50 soman at 24-h intervals, the low density ribosomes appeared as the predominant fraction whereas the activity of mRNA in all cell-free system was significantly impaired. It is concluded that soman intoxication expresses a stimulatory or inhibitory effect on the processes of protein synthesis in the rat brain, depending on the dose schedule of soman administration.

Effect of nicardipine on the isolated uterus and other smooth muscles of the rat.

Increasing concentrations of nicardipine were found to inhibit various types of muscular activation (electrical stimulation, acetylcholine, oxytocin, potassium chloride), as well as the spontaneous rhythmic activity of the isolated rat uterus. The degree of the inhibitory effect of nicardipine depends on the type of activation. Nicardipine showed an exceptionally high efficacy in inhibiting contractions induced by electrical stimulation and of spontaneous rhythmic activity. For inhibition of these contractions, even femtomolar concentrations of nicardipine were sufficient. The relaxant effect of nicardipine depends on the concentration of extracellular calcium and the temperature of the medium. Nicardipine shows high selectivity for the uterine smooth muscle because even in very high concentrations it exerts an insignificant relaxation of the other isolated smooth muscles (oesophagus, bladder, colon descendens) as well as of the isolated intercostal muscle of the rat. Our experiments indicate that nicardipine might have a role in the therapy of premature delivery and abortion because of its great selectivity for the uterine smooth muscle. Nicardipine causes a stronger inhibition of the tonic than of the phasic component of contraction induced by potassium chloride and oxytocin. These findings suggest that potassium chloride and oxytocin act through various populations of calcium channels.

Phrenic nerve-diaphragm preparation in situ for studying the detoxification of soman in the rat liver.

Detoxification of soman (1,2,2'-trimethylpropyl methylphosphonofluoridate) in the liver was studied in the rat phrenic nerve-diaphragm preparation in situ. Contractions of diaphragm induced by electrical stimulation of the phrenic nerve were continuously recorded. Twitch height depression caused by soman was influenced by the route of application (portal or jugular vein) indicating its rate of detoxification in the liver. Pretreatment with phenobarbital reduced, whereas previous application of tri-O-cresyl phosphate (TOCP) enhanced, effectiveness of soman administered i.p. Possible mechanisms of detoxification and the features of the method are discussed.

Soman intoxication-induced increase in the levels of mRNAs coding for acute phase reactants.

The effect of lethal and repetitive sublethal soman intoxication on the composition of rat liver mRNA was examined by cell-free translation and hybridization. It was found that lethal as well as sustained sublethal soman poisoning of rats elicited a typical acute phase response as judged by a several-fold increase in levels of mRNAs coding for the major acute phase proteins and the vast number of systemic and metabolic changes creating the acute phase response should be taken into account when the metabolic events during the recovery from organophosphate intoxication are under consideration.