Examining linkages among multiple sustainable development outcomes: does the productive safety net program increase on-farm agrobiodiversity?

In Ethiopia, on-farm agrobiodiversity and the Productive Safety Net Program (PSNP) play a key role in building smallholders' resilience. However, the impact of PSNP on on-farm agrobiodiversity is not yet well investigated. In this paper, we develop an analytical framework that links PSNP participation to on-farm agrobiodiversity. Both diverse farming systems and PSNP require labour inputs while providing income stabilization, which might result in a negative relationship between the two. Conversely, higher income from PSNP might allow farmers to increase their long-term on-farm investments, as opposed to the strategies oriented toward the highest immediate profit or calorie intake outcome. We base our empirical analysis on the World Bank's Ethiopian Socioeconomic Survey, a panel dataset encompassing nearly 3000 respondents and a Tobit model, based on Difference-in-Difference and the Propensity-Score Matching methods. We find that Ethiopia's PSNP has a negative impact on farm labour input, both in terms of labour intensity and duration. Furthermore, our results show that participation in the program is associated, on average, with lower on-farm crop diversity. We conclude that the PSNP participation may be crowding-out production stabilizing farming activities, such as intercropping or cover cropping, that are more labour intensive. Our findings call for embedding tools in the new phase of the PSNP (2021-2025) that could incentivise on-farm resilience-oriented investments, in particular leading to higher crop diversification.

Application Of The Enzymatic Debridement Of Burn Wounds In Patients During The Covid-19 Epidemic.

The unfolding pandemic necessitated optimalization of treatment methods and assurance of the highest precautionary standards to prevent transmission of COVID-19 to burn patients. One of them included an expanded access treatment with the minimally invasive method - enzymatic burn wound debridement using Nexobrid concentrate. The study assessed the effectiveness and usefulness of the expanded treatment project using enzymatic burn wound debridement with Nexobrid concentrate in patients (n=11) during the pandemic (2020) when compared with the results of the same method in a corresponding period of 2019. The concentrate was applied to the wound on the third day following injury at the latest. All patients were treated with the same accepted standards, including initial debridement of the wound, application of Nexobrid concentrate, and removal of devitalized tissue and dressing. Clinical visual assessment of the wound sites confirmed successful debridement of dead tissue following the application of the concentrate. No allergic or adverse reaction, nor significant deterioration of CBC parameters were observed in any patient. Although surgical excision of necrosis is recognized as the method of choice, enzymatic wound debridement using Nexobrid concentrate may contribute to a reduction in epidemiological risk when treating burn patients for several reasons; the procedure can be performed at the patient's bedside, it limits the number of required surgeries, helps to improve medical equipment and supplies management, and saves human resources.

La pandémie incontrôlée a nécessité une optimisation du traitement et des précautions d'hygiène maximales vis à vis des brûlés. Une d'entre elles consistait en l'utilisation de méthodes peu invasives dont l'excision enzymatique au Nexobrid . Cette étude compare l'efficacité et l'utilité l'utilisation larga manu de Nexobrid chez 11 patients pendant la période COVID (2020), comparée à son utilisation habituelle dans la période précédente. Ils bénéficiaient tout du même protocole à savoir nettoyage des plaies, application du Nexobrid au plus tard à J3 puis dépose du tissu nécrotique avec le pansement, confirmé par l'examen de la plaie. Nous n'avons observé ni allergie ni anomalie hématologique. Bien que la technique chirurgicale reste le traitement de référence, l'excision enzymatique peut limiter le risque épidémique qui y est lié car elle peut être réalisée au lit du patient, car elle diminue le nombre d'interventions chirurgicales, car elle permet d'améliorer les équipements, car elle diminue le nombre d'intervenants.

L-histidine is a beneficial adjuvant for antiepileptic drugs against maximal electroshock-induced seizures in mice.

Endogenous histamine has been reported to be involved in regulation of seizure susceptibility. Enhancement of histamine neurotransmission engendered by L-histidine treatment produces anticonvulsant effects in experimental animals. The present study investigated the influence of L-histidine on the protective effects of carbamazepine and phenytoin against maximal electroshock-induced seizures in mice.L-Histidine, administered at the doses that did not influence the threshold for electroconvulsions (250-500 mg/kg), enhanced by nearly 30% the protective effects of carbamazepine against maximal electroshock-induced seizures. D-Histidine (1000 mg/kg), an inactive isomer of histidine, was without any effect in this regard. L-Histidine (500 mg/kg) also augmented the protective effects of phenytoin. Importantly, the enhancement of the anticonvulsant effects of these antiepileptic drugs produced by L-histidine co-administration was not associated with augmentation of their unwanted effects on memory and motor performance. A pharmacokinetic interaction was also excluded since the free plasma levels of these antiepileptics remained unchanged in the presence of L-histidine. It may be suggested that L-histidine could serve as a beneficial adjuvant for selected antiepileptic drugs.

A potential anti-asthmatic drug, CR 2039, enhances the anticonvulsive activity of some antiepileptic drugs against pentetrazol in mice.

CR 2039 (4-(1H-tetrazol-5-yl)-N-[4-(1H-tetrazol-5-yl]phenylbenzam ide), in doses of 10, 20, and 100 mg/kg i.p., did not modify the seizure pattern observed after subcutaneous pentetrazol, administered at its CD97 of 90 mg/kg for the clonic phase. However, when combined with antiepileptic drugs, this phenylbenzamide derivative (20 mg/kg) converted the subprotective doses of ethosuximide (100 mg/kg) or valproate (100 mg/kg) against the clonic phase into anticonvulsive ones. The protection observed was comparable to that noted after doubling the doses of these antiepileptics. Also, a combination of valproate (100 mg/kg) with CR 2039 (10 mg/kg) resulted in a clear-cut protection against clonic seizures induced by pentetrazol. The protective efficacy of clonazepam was not affected by the phenylbenzamide derivative up to 40 mg/kg. The potentiation of the anticonvulsive activity of ethosuximide or valproate was not accompanied by increased adverse effects, evaluated in the chimney test (motor coordination) and passive avoidance task (long-term memory). Finally, CR 2039 (20 mg/kg) did not alter the plasma levels of the antiepileptic drugs studied, which speaks against a pharmacokinetic mechanism in the observed results. In conclusion, CR 2039 seems devoid of a hazardous influence of the anti-asthmatic drug, aminophylline, on the anticonvulsive effects of conventional antiepileptics.

Effect of non-steroidal anti-inflammatory drugs on the anticonvulsive activity of valproate and diphenylhydantoin against maximal electroshock-induced seizures in mice.

Prostaglandins and their inhibitors may affect convulsive phenomena. Thus, the aim of this study was to examine possible interactions between non-steroidal anti-inflammatory drugs and two conventional antiepileptic drugs in terms of their anticonvulsive activity and side-effects. Also, the plasma levels of antiepileptics were measured in order to delineate possible pharmacokinetic interactions. The following non-steroidal anti-inflammatory drugs (NSAIDs) were studied: acetylsalicylic acid, ibuprofen, indomethacin, metamizole, paracetamol and piroxicam. None of these drugs affected the threshold for electroconvulsions. However, all NSAIDs studied enhanced the protective activity of valproate magnesium against maximal electroshock-induced seizures. Only ibuprofen and piroxicam enhanced the anticonvulsive activity of diphenylhydantoin. Ibuprofen decreased the ED50 value of valproate (for the induction of motor impairment) in the rotorod test, whilst piroxicam reduced the ED50 value of valproate in rotorod and chimney tests. Diphenylhydantoin combined with either ibuprofen or piroxicam did not cause any motor impairment in these tests. The total plasma level of valproate and free plasma level of diphenylhydantoin remained unchanged in the presence of all studied NSAIDs. These data demonstrate that NSAIDs could enhance the protective activity of antiepileptics. However, in case of valproate it may be associated with the severe side effects.

GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] and the anticonvulsive activity of conventional antiepileptics against pentetrazol in mice.

Excitatory amino acids participate in the generation of seizure activity. Consequently, the effects of GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride], an antagonist of glutamate-mediated events, on the protective activity of conventional antiepileptic drugs against pentetrazol were studied. GYKI 52466 (up to 10 mg/kg, i.p.) did not affect the clonic phase of pentetrazol (injected s.c. at its CD97 of 90 mg/kg) convulsions. Only the antipentetrazol activity of valproate (100 mg/kg) was enhanced by GYKI 52466 (10 mg/kg)--the percentage of mice protected was significantly increased from 20 to 90%. The anticonvulsive activity of clonazepam (at 0.01), ethosuximide (at 50), and phenobarbital (at 2.5 mg/kg) was not modified by GYKI 52466 (up to 10 mg/kg). The combination of valproate (100 mg/kg) with GYKI 52466 (10 mg/kg) did not affect the performance of mice evaluated in the chimney test. However, this combination resulted in significant memory deficits, measured in the passive avoidance task. In no case did GYKI 52466 (10 mg/kg) affect either total or free plasma levels of antiepileptic drugs (as measured by immunofluorescence), so a pharmacokinetic interaction is not probable. Finally, the interaction of the non-NMDA receptor antagonist with antiepileptic drugs does not seem promising in the pentetrazol test, recognized as a model of human myoclonic epilepsy.

Influence of a potential anti-asthmatic drug, CR 2039, upon the anticonvulsive activity of conventional antiepileptics against maximal electroshock-induced seizures in mice.

CR 2039 [[4-(1H-tetrazol-5-yl)-N-(4-(1H-tetrazol-5-yl]phenylbenza m ide], in doses of 10, 50, and 100 mg/kg i.p., significantly elevated the threshold for electroconvulsions, increasing the CS50 (current strength 50% in mA) values from 6.3 to 7.2, 7.5, and 7.6 mA, respectively. When combined with carbamazepine, diphenylhydantoin, or valproate, CR 2039 (5 and 10 mg/kg) potentiated the anticonvulsive action of these antiepileptics against maximal electroshock-induced convulsions which was reflected by significant decreases in the respective ED50s (in mg/kg). The protective efficacy of phenobarbital was not affected by the phenylbenzamide derivative. The potentiation of the anticonvulsive activity of three antiepileptics was not accompanied by increased adverse effects, evaluated in the chimney test (motor coordination) and passive avoidance task (long-term memory). Finally, CR 2039 (10 mg/kg) did not alter the plasma levels of the antiepileptic drugs studied which speaks against a pharmacokinetic mechanism in the observed results. It is concluded that CR 2039 may prove a safer anti-asthmatic drug for the use in epileptic patients than aminophylline which, either acutely or chronically, considerably impaired the anticonvulsive activity of conventional antiepileptics.

Influence of aminophylline and 8-(p-sulfophenyl)theophylline on the anticonvulsive action of diphenylhydantoin, phenobarbital, and valproate against maximal electroshock-induced convulsions in mice.

Aminophylline (theophylline2.ethylenediamine) in the dose of 12.5 mg/kg (i.p.) was ineffective upon all antiepileptic drugs studied and at the higher dose of 25 mg/kg, impaired the anticonvulsant action of phenobarbital and valproate against maximal electroshock in mice. The protection offered by diphenylhydantoin was diminished by aminophylline at 50 mg/kg (0.238 mmol of anhydrous theophylline/kg). In contrast, 8-(p-sulfophenyl)theophylline (a theophylline derivative unable to cross the blood-brain barrier) in the dose of 80 mg/kg (0.238 mmol/kg) did not influence the protective activity of diphenylhydantoin, phenobarbital, and valproate. It might be concluded that the aminophylline-induced impairment of the anticonvulsant action of common antiepileptic drugs results from the central effects of this methylxanthine.

Synthesis and search for anticonvulsive and hypoglycemic properties of novel 5-benzylidene derivatives of 3-o-chloro- and 3-o-methylbenzoyl-2-thiohydantoin.

14 new benzylidene derivatives of 3-o-chloro- and 3-o-methylbenzoyl-2 thio hydantoin were synthesized. Their chemical structure was confirmed by IR, NMR and mass spectroscopy. Compounds 1-14 were tested for their anticonvulsant and hypoglycemic activity. Their toxicity was low and they showed only weak activity in tests for anticonvulsive and hypoglycemic properties.

Comparison of some properties of rubidomycine and its four derivatives.

In the experiments performed on Albino-Swiss mice and Wistar rats it was found that newly synthesized anthracyclines were less toxic and possessed similar pharmacological properties as rubidomycine. Only in some tests their activity was weaker or sometimes different.

comparison of pharmacological properties of cyclophosphamide and its enantiomers.

Comparison of pharmacological properties of commercial racemic Cyclophosphamide and its D- and L-enantiomers was performed in experiments on mice and rats. Acute toxicity, behavioral screening tests and the effects of subchronic treatment (influence on body mass, the increase of the mass of internal organs, mortality, morphology of peripheral blood, biochemical investigations of blood plasma, microscopic evaluation of liver and bladder) were taken into account. Summarized results revealed the most pronounced toxicity of D-cyclophosphamide. L-enantiomer was more toxic when compared with racemate. As several reports in literature confirmed the greatest antineoplastic activity of L-form in animals, the suggestion of further clinical investigation of levorotatory form as a separate preparation has been put forward.

Effect of combined treatment of diphenylhydantoin with clonazepam and chlordiazepoxide on the threshold for maximal electroconvulsions in mice.

The anticonvulsant effect of either clonazepam (0.2-6.4 mg/kg) or chlordiazepoxide (2.5-40 mg/kg) alone or in combination with diphenylhydantoin (4-16 mg/kg) was studied against electroconvulsions in mice. All drugs were injected intraperitoneally, diphenylhydantoin - 75 min and the benzodiazepines - 60 min before the test. Adding either clonazepam or chlordiazepoxide (in doses moderately increasing the convulsive threshold) was more effective than doubling the dose of diphenylhydantoin. Both the interaction between benzodiazepines and diphenylhydantoin at the level of the receptor for picrotoxin-barbiturates and benzodiazepine-induced potentiation of specific diphenylhydantoin binding are likely to contribute to the observed phenomenon. On the other hand, a diphenylhydantoin-induced increase in the total number of specific benzodiazepine binding sites seems of minor importance since clonazepam (with a high affinity for these sites) and chlordiazepoxide (with a low affinity) were equipotent in the enhancement of the combined treatment efficacy.

Effect of combined GABA-ergic and dopaminergic stimulation on the action of some antiepileptic drugs in pentetrazol-induced convulsions.

Apomorphine (up to 10 mg/kg) and amantadine (up to 100 mg/kg) did not affect pentetrazol-induced convulsions in mice. One of two GABA-ergic agonists tested, baclofen (10 mg/kg), decreased seizure susceptibility (except for the clonic phase) while another, amino-oxyacetic acid (up to 20 mg/kg) had no effect. Combined treatment was most effective in the case of baclofen (5 mg/kg) and amantadine (100 mg/kg) where number of animals with tonic seizures was decreased. Dopaminergic stimulation did not modify the action of some anticonvulsants tested. However, GABA-ergic stimulation resulted in a marked potentiation of the action of carbamazepine (10 mg/kg) and acetazolamide (20 mg/kg), being less pronounced in reference to diazepam (0 . 5 mg/kg) in lefadol (20 mg/kg). On the other hand, combined treatment with GABA-ergic and dopaminergic stimulants was shown to enhance the action of carbamazepine and acetazolamide, but not in the clonic phase. The obtained results suggest effectiveness of GABA-ergic stimulation in the case of all drugs tested and the combined treatment with GABA-ergic and dopaminergic agonists in potentiating the effects of some antiepileptics.

Effect of dopaminergic and GABA-ergic drugs given alone or in combination on the anticonvulsant action of phenobarbital and diphenylhydantoin in the electroshock test in mice.

In the electroshock test--taking hind-limb tonic extension as the end point--apomorphine (10 mg/kg) exerted no effect on the anticonvulsant action of phenobarbital (PB; 20 mg/kg) or diphenylhydantoin (DPH; 8 mg/kg); amantadine (25 and 100 mg/kg) decreased that of DPH, while L-DOPA (500 mg/kg) and d,l-amphetamine (10 mg/kg) potentiated the action of both anticonvulsants. Fluphenazine (4 mg/kg) had no influence on the effects of the two anticonvulsants, but haloperidol lessened that of DPH. All GABA-ergic stimulants used, i.e., gamma-hydroxybutyric acid (GHBA/250 mg/kg), baclofen (2.5 and 10 mg/kg) and aminooxoacetic acid (AOAA; 15 and 20 mg/kg) potentiated the action of PB; the action of DHP was unaffected by these drugs except for AOAA (20 mg/kg). The combined treatment with dopaminergic and GABA-ergic stimulants, being ineffective in terms of anticonvulsant activity, resulted in a marked potentiation of the action of the anticonvulsants tested in this study. The most distinct potentiation was noted in the case of PB, baclofen (1 mg/kg), and amantadine (25 mg/kg).