Cannabidiol Interacts Antagonistically with Cisplatin and Additively with Mitoxantrone in Various Melanoma Cell Lines-An Isobolographic Analysis.

The medical application of cannabidiol (CBD) has been gathering increasing attention in recent years. This non-psychotropic cannabis-derived compound possesses antiepileptic, antipsychotic, anti-inflammatory and anxiolytic properties. Recent studies report that it also exerts antineoplastic effects in multiple types of cancers, including melanoma. In this in vitro study we tried to reveal the anticancer properties of CBD in malignant melanoma cell lines (SK-MEL 28, A375, FM55P and FM55M2) administered alone, as well as in combination with mitoxantrone (MTX) or cisplatin (CDDP). The effects of CBD on the viability of melanoma cells were measured by the MTT assay; cytotoxicity was determined in the LDH test and proliferation in the BrdU test. Moreover, the safety of CBD was tested in human keratinocytes (HaCaT) in LDH and MTT tests. Results indicate that CBD reduces the viability and proliferation of melanoma-malignant cells and exerts additive interactions with MTX. Unfortunately, CBD produced antagonistic interaction when combined with CDDP. CBD does not cause significant cytotoxicity in HaCaT cell line. In conclusion, CBD may be considered as a part of melanoma multi-drug therapy when combined with MTX. A special attention should be paid to the combination of CBD with CDDP due to the antagonistic interaction observed in the studied malignant melanoma cell lines.

Comparison of the Anticancer Effects of Arvanil and Olvanil When Combined with Cisplatin and Mitoxantrone in Various Melanoma Cell Lines-An Isobolographic Analysis.

Due to the unique structures of arvanil and olvanil, the drugs combine certain properties of both cannabinoids and vanilloids, which makes them able to stimulate both TPRV1 and CB1 receptors and causes them to be interesting agents in the setting of carcinoma treatment. The aim of this study was to investigate the cytotoxic and anti-proliferative effects of arvanil and olvanil when administered alone and in combination with cisplatin (CDDP) and mitoxantrone (MTX), using various primary (A375, FM55P) and metastatic (SK-MEL 28, FM55M2) human malignant melanoma cell lines. The results indicate that both arvanil and olvanil inhibited (dose-dependently) the viability and proliferation of various malignant melanoma cells, as demonstrated by MTT and BrdU assays. The safety profile of both arvanil and olvanil tested in human keratinocytes (HaCaT) and normal human melanocytes (HEMa-LP) revealed that neither arvanil nor olvanil caused significant cytotoxicity in HaCaT and HEMa-LP cell lines in LDH and MTT assays. Isobolographically, it was found that both arvanil and olvanil exerted additive interactions with MTX and antagonistic interactions with CDDP in the studied malignant melanoma cell lines. In conclusion, the combinations of arvanil or olvanil with MTX may be considered as a part of melanoma multi-drug therapy; however, the combination of these compounds with CDDP should be carefully considered due to the antagonistic interactions observed in the studied malignant melanoma cell lines.

Effectiveness of the Functional Movement Screen for assessment of injury risk occurrence in football players.

The aim of the study was to determine whether the Functional Movement Screen (FMS) test carried out among young boys practising football training identifies previous injuries. Sixty-five boys aged 12-13 years, who had regularly practised football in an academy for at least 3 years, were recruited and divided into two groups: an injured group (IG), consisting of players who had experienced at least one injury in the past (n + 25, age 12.32 ± 0.48) and a non-injured group (non-IG), a control group, made up of athletes with no injuries to the musculoskeletal system (n = 40, age 12.25 ± 0.49). Seven FMS tests were used to rate the functional fitness level as a part of the FMS tool. Significant differences between the total scores of the FMS tests (p < 0.001, r = 0.54) were documented. Higher scores in the FMS test were observed in the control group (M = 16.58, SD = 2.04) than in the study group (M = 14.20, ± SD = 1.96). The FMS test is an effective diagnostic tool to identify previous injuries among young football players.

Anticonvulsant Effectiveness and Neurotoxicity Profile of 4-butyl-5-[(4-chloro-2-methylphenoxy)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) in Mice.

Protective (antiseizure) effects of 4-butyl-5-[(4-chloro-2-methylphenoxy)-methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) and acute neurotoxic effects were determined in the tonic-clonic seizure model and rotarod test in mice. The interaction profile of four classic antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) with TPL-16 was also determined in the tonic-clonic seizure model in mice. The protective effects of TPL-16 from tonic-clonic seizures (as ED50 values) and acute neurotoxic effects of TPL-16 (as TD50 values) were determined in 4 pretreatment times (15, 30, 60 and 120 min after its i.p. administration), in adult male albino Swiss mice. The interaction profile of TPL-16 with carbamazepine, phenobarbital, phenytoin and valproate in the tonic-clonic seizure model was determined with isobolographic analysis. Total concentrations of carbamazepine, phenobarbital, phenytoin and valproate were measured in the mouse brain homogenates. The candidate for novel antiepileptic drug (TPL-16) administered separately 15 min before experiments, has a beneficial profile with protective index (as ratio of TD50 and ED50 values) amounting to 5.58. The combination of TPL-16 with valproate produced synergistic interaction in the tonic-clonic seizure model in mice. The combinations of TPL-16 with carbamazepine, phenobarbital and phenytoin produced additive interaction in terms of protection from tonic-clonic seizures in mice. None of the total brain concentrations of classic AEDs were changed significantly after TPL-16 administration in mice. Synergistic interaction for TPL-16 with valproate and the additive interaction for TPL-16 with carbamazepine, phenobarbital and phenytoin in the tonic-clonic seizures in mice allows for recommending TPL-16 as the promising drug for further experimental and clinical testing.

Synergy, Additivity, and Antagonism between Cisplatin and Selected Coumarins in Human Melanoma Cells.

(1) Cisplatin (CDDP) is used in melanoma chemotherapy, but it has many side effects. Hence, the search for natural substances that can reduce the dose of CDDP, and CDDP-related toxicity, is highly desired. Coumarins have many biological properties, including anticancer and antiproliferative effects. (2) An in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on two human melanoma cell lines (FM55P and FM55M2) examined the antitumor properties of CDDP and five naturally occurring coumarins (osthole, xanthotoxin, xanthotoxol, isopimpinellin, and imperatorin). The antiproliferative effects produced by combinations of CDDP with the coumarins were assessed using type I isobolographic analysis. (3) The most potent anticancer properties of coumarins were presented by osthole and xanthotoxol. These compounds were characterized by the lowest median inhibitory concentration (IC50) values relative to the FM55P and FM55M2 melanoma cells. Isobolographic analysis showed that for both melanoma cell lines, the combination of CDDP and osthole exerted synergistic and additive interactions, while the combination of CDDP and xanthotoxol exerted additive interactions. Combinations of CDDP with xanthotoxin, isopimpinellin, and imperatorin showed antagonistic and additive interactions in two melanoma cell lines. (4) The combination of CDDP and osthole was characterized by the most desirable synergistic interaction. Isobolographic analysis allows the selection of potential candidates for cancer drugs among natural substances.

Interactions among Lacosamide and Second-Generation Antiepileptic Drugs in the Tonic-Clonic Seizure Model in Mice.

Combination therapy with two or three antiseizure medications (ASMs) is sometimes a preferred method of treatment in epilepsy patients. (1) Background: To detect the most beneficial combination among three ASMs, a screen test evaluating in vivo interactions with respect to their anticonvulsant properties, was conducted on albino Swiss mice; (2) Methods: Classification of interactions among lacosamide (LCM) and selected second-generation ASMs (lamotrigine (LTG), pregabalin (PGB), oxcarbazepine (OXC), and topiramate (TPM)) was based on the isobolographic analysis in the mouse maximal electroshock-induced seizure (MES) model. Interactions among LCM and second-generation ASMs were visualized using a polygonogram; (3) Results: In the mouse MES model, synergy was observed for the combinations of LCM + TPM + PGB and LCM + OXC + PGB. Additivity was reported for the other combinations tested i.e., LCM + LTG + TPM, LCM + LTG + PGB, LCM + LTG + OXC, and LCM + OXC + TPM in this seizure model. No adverse effects associated with triple ASM combinations, containing LCM and second-generation ASMs were observed in mice; (4) Conclusions: The combination of LCM + TPM + PGB was the most beneficial combination among the tested in this study, offering synergistic suppression of tonic-clonic seizures in mice subjected to the MES model. Both the isobolographic analysis and polygonogram method can be recommended for experimental epileptology when classifying interactions among the ASMs.

Influence of dronedarone (a class III antiarrhythmic drug) on the anticonvulsant potency of four classical antiepileptic drugs in the tonic-clonic seizure model in mice.

Increasing evidence indicates that some antiarrhythmic drugs play a pivotal role in seizures, not only in vivo studies on animals, but also in clinical trials. Some of these antiarrhythmic drugs potentiate or alleviate the anticonvulsant action of the classical antiepileptic drugs. The aim of this study was to determine the influence of dronedarone (DRO-a multichannel blocker belonging to the class III of antiarrhythmic drugs) on the anticonvulsant effects of four standard antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) in the tonic-clonic seizure model in mice. Potential acute adverse effects exerted by the antiepileptic drugs combined with DRO were evaluated in three behavioral tests (chimney, grip-strength and passive avoidance). To confirm the nature of interaction, total brain concentrations of antiepileptic drugs were measured. DRO (50 mg/kg, i.p.) significantly reduces the anticonvulsant potency of phenytoin (P < 0.05), having no impact on that of carbamazepine, phenobarbital and valproate in the tonic-clonic seizure model in mice. DRO (50 mg/kg) neither changed total brain concentrations of phenytoin in mice, nor affected normal behavior in experimental animals subjected to the chimney, grip-strength and passive avoidance tests. In conclusion, DRO should not be combined with phenytoin because it reduced the anticonvulsant effects of the latter drug in experimental animals. The combined administration of DRO with carbamazepine, phenobarbital and valproate resulted in neutral interaction between these drugs in the tonic-clonic seizure model in mice.

Beneficial Combination of Lacosamide with Retigabine in Experimental Animals: An Isobolographic Analysis.

BACKGROUND/AIM: To isobolographically determine the types of interactions that occur between retigabine and lacosamide (LCM; two third-generation antiepileptic drugs) with respect to their anticonvulsant activity and acute adverse effects (sedation) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male Swiss mice. METHODS: Type I isobolographic analysis for nonparallel dose-response effects for the combination of retigabine with LCM (at the fixed-ratio of 1:1) in both the MES and chimney test in mice was performed. Brain concentrations of retigabine and LCM were measured by high-pressure liquid chromatography (HPLC) to characterize any pharmacokinetic interactions occurring when combining these drugs. RESULTS: Linear regression analysis revealed that retigabine had its dose-response effect line nonparallel to that of LCM in both the MES and chimney tests. The type I isobolographic analysis illustrated that retigabine combined with LCM (fixed-ratio of 1:1) exerted an additive interaction in the mouse MES model and sub-additivity (antagonism) in the chimney test. With HPLC, retigabine and LCM did not mutually change their total brain concentrations, thereby confirming the pharmacodynamic nature of the interaction. CONCLUSION: LCM combined with retigabine possesses a beneficial preclinical profile (benefit index ranged from 2.07 to 2.50) and this 2-drug combination is worth recommending as treatment plan to patients with pharmacoresistant epilepsy.

Influence of Ivabradine on the Anticonvulsant Action of Four Classical Antiepileptic Drugs Against Maximal Electroshock-Induced Seizures in Mice.

Although the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in neuronal excitability and synaptic transmission is still unclear, it is postulated that the HCN channels may be involved in seizure activity. The aim of this study was to assess the effects of ivabradine (an HCN channel inhibitor) on the protective action of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) against maximal electroshock-induced seizures in mice. Tonic seizures (maximal electroconvulsions) were evoked in adult male albino Swiss mice by an electric current (sine-wave, 25 mA, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles of the combinations of ivabradine with classical antiepileptic drugs were measured in mice along with total brain antiepileptic drug concentrations. Results indicate that ivabradine (10 mg/kg, i.p.) significantly enhanced the anticonvulsant activity of valproate and considerably reduced that of phenytoin in the mouse maximal electroshock-induced seizure model. Ivabradine (10 mg/kg) had no impact on the anticonvulsant potency of carbamazepine and phenobarbital in the maximal electroshock-induced seizure test in mice. Ivabradine (10 mg/kg) significantly diminished total brain concentration of phenytoin and had no effect on total brain valproate concentration in mice. In conclusion, the enhanced anticonvulsant action of valproate by ivabradine in the mouse maximal electroshock-induced seizure model was pharmacodynamic in nature. A special attention is required when combining ivabradine with phenytoin due to a pharmacokinetic interaction and reduction of the anticonvulsant action of phenytoin in mice. The combinations of ivabradine with carbamazepine and phenobarbital were neutral from a preclinical viewpoint.

Synergistic Interaction of Retigabine with Levetiracetam in the Mouse Maximal Electroshock-Induced Seizure Model: A Type II Isobolographic Analysis.

BACKGROUND/AIMS: To assess interactions between retigabine and levetiracetam in suppressing maximal electroshock-induced tonic seizures in Albino Swiss mice, type II isobolographic analysis was used. Total brain antiepileptic drug concentrations were measured with high pressure liquid chromatography. RESULTS: The combinations of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; p < 0.05) in terms of seizure suppression, while the combinations at the fixed-ratios of 1:1 and 1:2 were additive. No pharmacokinetic changes in total brain concentrations of levetiracetam and retigabine were documented, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse maximal electroshock-induced tonic seizure model. CONCLUSION: The combination of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 appears to be particularly beneficial combination exerting supra-additive interaction in suppressing maximal electroshock-induced tonic seizures.

Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB 2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model.

The aim of this study was to characterize the influence of WIN 55,212-2 (WIN--a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Drug-related adverse effects were ascertained by use of the chimney test (evaluating motor performance), step-through passive avoidance task (assessing learning) and grip-strength test (evaluating skeletal muscular strength). Total brain concentrations of antiepileptic drugs were measured by fluorescence polarization immunoassay to ascertain any pharmacokinetic contribution to the observed antiseizure effect. Results indicate that WIN (5 mg/kg, administered intraperitoneally) significantly enhanced the anticonvulsant action of clonazepam (P < 0.001), phenobarbital (P < 0.05) and valproate (P < 0.05), but not that of clobazam in the mouse 6 Hz model. Moreover, WIN (2.5 mg/kg) significantly potentiated the anticonvulsant action of clonazepam (P < 0.01), but not that of clobazam, phenobarbital or valproate in the 6 Hz test in mice. None of the investigated combinations of WIN with antiepileptic drugs was associated with any concurrent adverse effects with regard to motor performance, learning or muscular strength. Pharmacokinetic experiments revealed that WIN had no impact on total brain concentrations of antiepileptic drugs in mice. These preclinical data would suggest that WIN in combination with clonazepam, phenobarbital and valproate is associated with beneficial anticonvulsant pharmacodynamic interactions in the mouse 6 Hz-induced psychomotor seizure test.

Imperatorin interacts additively with novel antiseizure medications in the mouse maximal electroshock-induced seizure model: an isobolographic transformation.

BACKGROUND: Anticonvulsant effects of imperatorin (IMP) have been experimentally confirmed earlier, but no information is available on the interaction profiles of this naturally occurring coumarin when combined with novel antiseizure medication (ASMs). This study aimed to determine the effects of IMP on the anticonvulsant effects of lacosamide (LCM), oxcarbazepine (OXC), pregabalin (PGB), and topiramate (TPM) in the maximal electroshock-induced seizure (MES) model in mice. METHODS: The anticonvulsant effects exerted by novel ASMs (LCM, OXC, PGB, and TPM) when combined with constant doses of IMP (25 and 50 mg/kg) underwent isobolographic transformation to precisely classify the observed interactions in the mouse MES model. Total brain concentrations of ASMs were measured with high-pressure liquid chromatography to exclude the pharmacokinetic nature of interactions among IMP and the tested ASMs. RESULTS: IMP (50 mg/kg) significantly enhanced (p < 0.01) the anticonvulsant potency of LCM, OXC, PGB, and TPM in the mouse MES model. IMP (25 mg/kg) mildly potentiated the anticonvulsant action of LCM, OXC, PGB, and TPM, but no statistical significance was reported for these combinations. The isobolographic transformation of data from the MES test revealed that the interactions of novel ASMs with IMP were additive. Moreover, IMP (50 mg/kg) did not affect the total brain content of any of the novel ASMs in experimental mice. CONCLUSIONS: The additive interactions of IMP with LCM, OXC, PGB, and TPM in the mouse MES model accompanied by no pharmacokinetic changes in the total brain content of ASMs are worthy of recommendation for further studies.

AM1172 (a hydrolysis-resistant endocannabinoid analog that inhibits anandamide cellular uptake) reduces the viability of the various melanoma cells, but it exerts significant cytotoxic effects on healthy cells: an in vitro study based on isobolographic analysis.

BACKGROUND: Despite great advances in our understanding of the impact of cannabinoids on human organism, many of their properties still remain undetermined, including their potential antineoplastic effects. This study was designed to assess the anti-proliferative and cytotoxic effects of AM1172 (a hydrolysis-resistant endocannabinoid analog that inhibits anandamide cellular uptake) administered alone and in combinations with docetaxel (DOCX), paclitaxel (PACX), mitoxantrone (MTX) and cisplatin (CDDP) on various human malignant melanoma A375, FM55P, SK-MEL 28 and FM55M2 cell lines. MATERIALS: In the MTT, LDH, and BrdU assays, the potency and safety of AM1172 when administered alone and in combinations with DOCX, PACX, MTX, and CDDP were determined. RESULTS: The isobolographic analysis revealed that combinations of AM1172 with PACX, DOCX, MTX, and CDDP exerted additive interactions, except for a combination of AM1172 with PACX in primary melanoma A375 cell line, for which synergy was observed (*p<0.05). Nevertheless, AM1172 when administered alone produced cytotoxic effects on healthy human melanocytes (HEMa-LP) and human keratinocytes (HaCaT), which unfortunately limits its potential therapeutic utility. CONCLUSIONS: AM1172 cannot be used separately as a chemotherapeutic drug, but it can be combined with PACX, DOCX, MTX, and CDDP, offering additive interactions in terms of the anti-proliferative effects in various malignant melanoma cell lines.

Effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on the protective action of various antiepileptic drugs in the maximal electroshock-induced seizure model: a type II isobolographic analysis.

The aim of this study was to characterize the interaction between 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ-an endogenous parkinsonism-preventing substance) and various antiepileptic drugs [AEDs: clonazepam (CZP), ethosuximide (ETS), gabapentin (GBP), levetiracetam (LEV), tiagabine (TGB) and vigabatrin (VGB)] in the mouse maximal electroshock (MES)-induced seizure model. Results indicate that 1-MeTHIQ in combination with CZP (at the fixed ratios of 50:1 and 25:1), ETS (1:10) and GBP (1:1, 1:2, 1:5 and 1:10) exerted supra-additive (synergistic) interactions in the mouse MES model. In contrast, 1-MeTHIQ in combination with CZP (200:1 and 100:1), ETS (1:1, 1:2 and 1:5), LEV and VGB (1:1, 1:2, 1:5 and 1:10), and TGB (200:1, 100:1, 50:1 and 25:1) produced additive interaction in the mouse MES model. Total brain AED concentrations were unaffected by 1-MeTHIQ, and inversely, CZP, ETS and GBP had no impact on total brain concentrations of 1-MeTHIQ, indicating pharmacodynamic nature of synergistic interactions between 1-MeTHIQ and the tested AEDs in the mouse MES model. In conclusion, the supra-additive interactions of 1-MeTHIQ with CZP (at the fixed ratios of 50:1 and 25:1), ETS (1:10) and GBP (1:1, 1:2, 1:5 and 1:10) in the mouse MES model appear to be particularly favorable combinations from a clinical viewpoint. The additive combinations of 1-MeTHIQ with CZP (100:1, 50:1), ETS (1:1, 1:2 and 1:5), LEV and VGB (1:1, 1:2, 1:5, and 1:10), and TGB (200:1, 100:1, 50:1 and 25:1) seem to be neutral and worthy of consideration in further clinical practice.

[Effects of work in childhood on health in the opinion of respondents from agricultural families]. / Wplyw pracy w dziecinstwie na zdrowie w opinii osób pochodzmcych z rodzin rolniczych.

BACKGROUND: The engagement of children in work is common in agricultural families. Work of children brings about cific benefits to both the family and the children; however, at the same time, it creates many hazards, including health risk. MATERIALS AND METHOD: The aim of the study was to determine current and delayed health effects among individuals who were engaged in agricultural activities in childhood. The study was conducted using the method of diagnostic survey questionnaire and covered a group of 482 adults from agricultural families. RESULTS: The majority of respondents expressed the opinion that work in childhood had no impact on their health. At the same time, 2/5 of respondents considered that work on their parents' farm exerted an effect on their health in childhood (current effects), whereas nearly 1/3 admitted that an engagement in work in childhood also affected their present state of health (delayed effects). In the respondents' opinion, overloading with work in childhood exerted an adverse effect on their health, and also resulted in health problems in adulthood. CONCLUSION: The engagement of children in agricultural work in a small amount of working time, and adjustment of assigned jobs to their capabilities brings about many health benefits with low health risk. In turn, the engagement of children in work from their youngest years and overloading them with work exerts an adverse effect on health, especially in later life.

Euthanasia in opinions of students of medicine.

INTRODUCTION AND OBJECTIVE: Euthanasia assumes the deliberate deprivation of life of another human being for the good of that person. At present, euthanasia is legally practiced in Holland, Belgium, Luxemburg, Columbia and Canada. In Poland, euthanasia is strictly prohibited. The aim of this work is to present the opinions of medical students about euthanasia. An anonymous questionnaire was conducted among first-year students of medicine at the Medical University of Lublin, Poland. MATERIAL AND METHODS: The anonymous questionnaire consisted of 35 questions that concerned three components of euthanasia attitude: knowledge, evaluation, and acceptance of its use. The study included 281 students of medicine (77.6% of all first-year students). RESULTS: Although euthanasia in Poland is legally prohibited, almost one-fifth of students of medicine expressed a positive attitude towards euthanasia, and over a quarter of students opted for its legalization. Only two independent variables, i.e., family size (number of children) and religious involvement of the respondents, differentiated both the overall assessment of euthanasia and the level of acceptance for its legalization. Non-religious people more often (43.3%) than religiously engaged people (6.4%) expressed positive opinions about euthanasia. CONCLUSIONS: The attitudes of students towards euthanasia are often inconsistent. There is a need to evaluate medical study programmes in the context of creating the right attitudes of future doctors towards euthanasia.

Assessment of functional capacity of the elderly.

INTRODUCTION AND OBJECTIVE: Ageing is a continuous, progressive process of functional reserve loss. Physical fitness and mental state have a significant impact on the functionality level of the elderly population. Assessing the degree elderly people's of independence regarding self-care is an important aspect of the Comprehensive Geriatric Assessment (CGA). The aim of the study was to assess the functional capacity of people over 65 years of age. MATERIAL AND METHODS: The study involved 312 patients in hospital wards across Lower Silesia, south-west Poland. The criteria for participation were as follows: providing informed consent to participate in the study, intellectual capacity to be interviewed, and age over 65. The study applied the diagnostic survey method, together with the use of the VAS, Barthel, IADL and GDS scales. RESULTS: Among the respondents, 59.94% were in a moderately severe condition according to the Barthel scale, average IADL score - 20.56 points; according to the GDS scale, 58.97% had no symptoms of depression. Respondents suffered from multiple chronic diseases, the most common of which were hypertension (71.47%); they also reported some medical issues, mainly back pain (47.44). Assessment of the correlation of the Barthel and GDS scales, as well as the IADL and GDS, revealed a significant and negative correlation at -0.49 and -0.50. Assessment of the correlation between the number of diseases and the Barthel scale was -0.49, the number of symptoms and the Barthel scale -0.4; pain severity and the Barthel scale -0.41, number of diseases and IADL -0.58, and number of symptoms and IADL -0.52. CONCLUSIONS: The greater the seniors' independence regarding instrumental activities of daily living, the weaker the symptoms of depression. Multimorbidity and experiencing pain impaired independence among the elderly.

Anticonvulsant effects of isopimpinellin and its interactions with classic antiseizure medications and borneol in the mouse tonic-clonic seizure model: an isobolographic transformation.

BACKGROUND: Overwhelming evidence indicates that some naturally occurring coumarins and terpenes are widely used in folk medicine due to their various therapeutic effects affecting the brain. Antiseizure medications (ASMs) are the principal treatment option for epilepsy patients, although some novel strategies based on naturally occurring substances are intensively investigated. This study was aimed at determining the influence of isopimpinellin (ISOP-a coumarin) when administered either separately or in combination with borneol (BOR-a monoterpenoid), on the antiseizure potencies of four classic ASMs (carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and valproate (VPA)) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MATERIALS: Tonic-clonic seizures were evoked experimentally in mice after systemic (ip) administration of the respective doses of ISOP, BOR, and classic ASMs. Interactions for two-drug (ISOP + a classic ASM) and three-drug (ISOP + BOR + a classic ASM) mixtures were assessed isobolographically in the mouse MES model. RESULTS: ISOP (administered alone) had no impact on the anticonvulsant potencies of four classic ASMs. Due to the isobolographic transformation of data, the combination of ISOP + VPA exerted an antagonistic interaction, whereas the two-drug mixtures of ISOP + CBZ, ISOP + PHT, and ISOP + PB produced additive interactions in the mouse MES model. The three-drug combinations of ISOP + BOR with CBZ and PHT produced additive interactions, while the three-drug combinations of ISOP + BOR with PB and VPA exerted synergistic interactions in the mouse MES model. CONCLUSIONS: The most intriguing interaction was that for ISOP + VPA, for which the addition of BOR evoked a transition from antagonism to synergy in the mouse MES model.

Evaluation of the quality of life of older people with diabetes.

INTRODUCTION AND OBJECTIVE: Diabetes is commonly classified as a chronic disease of affluence due to the frequency of its incidence and the rate of its spreading. The aim of the study was to evaluate the quality of life of geriatric patients with type 2 diabetes. MATERIAL AND METHODS: 294 seniors diagnosed with type 2 diabetes living in the Lower Silesian Province in south-western Poland took part in the study. The study used a self-developed questionnaire collecting clinical and socio-demographic data, the WHOQOL-Bref questionnaire, Acceptance of Illness Scale (AIS), Self-Care of Diabetes Inventory (SCODI) and the Geriatric Depression Scale (GDS). RESULTS: Significant relationships of QoL with BMI, level of education and place of residence, were observed. BMI was significantly negatively correlated with the psychological domain of functioning and the environmental functioning, the level of education was correlated with physical health, psychological and environmental functioning, while the place of residence was correlated with the perception of the QoL and environmental functioning. Acceptance of illness was positively correlated with the perception of QoL and one's physical health. The results of regression analyses in predicting QoL in all domains showed that all models were a good fit for the data (p < 0.001), and the single predictor was maintenance of self-care. The level of depression was negatively correlated to a statistically significant degree with the perception of QoL and one's health condition. CONCLUSIONS: BMI, level of education and place of residence had the highest impact on the quality of life of the participants. The quality of life of the participants improved with the increase in the acceptance of their illness. The higher the level of depression exhibited by the participants, the poorer they evaluated their quality of life.

Impact of isolation on the biopsychosocial functioning of older people with COVID-19.

INTRODUCTION: COVID-19 is a highly contagious coronavirus disease that has had a significant impact on the functioning of society. On 11 March 2020, due to the rapid spread of the virus, the WHO declared a global pandemic. By the end of 2021, 5 variants of SARS-CoV-2 had been identified since the beginning of the pandemic. The course of the disease varied depending on the age of the patients and the presence of possible comorbidities. Most patients were asymptomatic or sparsely symptomatic of the infection; however, in about 6% of cases, the course of the disease was critical. Typical symptoms of COVID-19 include: fever, muscle pain and headache, lack of smell and taste, cough, dyspnea, diarrhoea and nausea. According to epidemic guidelines, infected patients were subjected to isolation, which harmed their mental state, especially the elderly. OBJECTIVE: The aim of the study was to assess the impact of isolation on the biopsychosocial functioning of elderly patients with COVID-19. MATERIAL AND METHODS: The study was conducted among 360 elderly patients in hospital wards operating as a unit in a hospital complex dedicated to patients infected with the SARS-CoV-2 virus. Data were collected using standardized questionnaires: ADL Scale, IADL, GDS, SF-36 Quality of Life Scale, Multidimensional Scale of Perceived Social Support, and supplementary questions about, among others, the oxygen therapy provided, length of stay in the unit, and the support received from relatives. RESULTS: Almost half (48%) of the subjects received oxygen therapy, and 36% had a length of disease of 7-14 days. A correlation was observed between the quality of life and the above-mentioned factors. Correlations of quality of life indicators with the length of illness were moderate (except for the level of pain) and positive, meaning that the longer the patients were ill, the lower their quality of life. Correlations of disease severity were moderate for pain, vitality, and emotional limitations, while vital for physical functioning and limitations and general and mental health. The intensity of oxygen therapy was moderately correlated with physical and emotional limitations and general health and strongly correlated with physical functioning, vitality and mental health. Correlations between functional status and mental status of elderly patients were also studied. Analysis of variance showed that the constructed model was an excellent fit to the data, F = 37.14; p < 0.001, explaining 42% of the variance in the dependent variable (R2= 0.42). As many as 80% of the respondents felt that isolation harmed their well-being. Examining the impact of quality of life on their well-being showed that most of the associations tested were statistically significant, and all were positive. Associations of moderate strength were shown for physical functioning, physical limitations and general health, while strong associations were shown for vitality, emotional limitations and mental health. Pain complaints were associated with changes in well-being at the level of statistical trend (p = 0.055). This means that the lower the patients' quality of life, especially in terms of vitality and mental health, the more significant the impact of isolation on their well-being. The study also investigated the effect of social support on mental state. The model proved to be an excellent fit to the data, F = 5.91, p = 0.002, and explained 23% of the variance in the dependent variable (Adjusted R² = 0.23). At the same time, support from friends turned out to be the only significant predictor (Beta = 0.53), and this means that the more support the subjects received from them, the lower the level of depression they manifested. CONCLUSIONS: 1) The better the functional state of a senior and the support received from relatives, the lower the severity of depression. 2) The lower the quality of a senior's life, especially in terms of mental state, the greater the negative impact on his/her well-being in isolation. 3) The low quality of life of a senior increased the likelihood of depression. 4) The quality of life of older Covid-19 patients was higher in those without chronic disease. 5) The quality-of-life level was lower in patients with a more severe course of COVID-19, and longer duration of disease and oxygen therapy.