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1.
J Neurophysiol ; 132(1): 240-258, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38865217

RESUMEN

Muscle force is modulated by sequential recruitment and firing rates of motor units (MUs). However, discrepancies exist in the literature regarding the relationship between MU firing rates and their recruitment, presenting two contrasting firing-recruitment schemes. The first firing scheme, known as "onion skin," exhibits low-threshold MUs firing faster than high-threshold MUs, forming separate layers akin to an onion. This contradicts the other firing scheme, known as "reverse onion skin" or "afterhyperpolarization (AHP)," with low-threshold MUs firing slower than high-threshold MUs. To study this apparent dichotomy, we used a high-fidelity computational model that prioritizes physiological fidelity and heterogeneity, allowing versatility in the recruitment of different motoneuron types. Our simulations indicate that these two schemes are not mutually exclusive but rather coexist. The likelihood of observing each scheme depends on factors such as the motoneuron pool activation level, synaptic input activation rates, and MU type. The onion skin scheme does not universally govern the encoding rates of MUs but tends to emerge in unsaturated motoneurons (cells firing < their fusion frequency that generates peak force), whereas the AHP scheme prevails in saturated MUs (cells firing at their fusion frequency), which is highly probable for slow (S)-type MUs. When unsaturated, fast fatigable (FF)-type MUs always show the onion skin scheme, whereas S-type MUs do not show either one. Fast fatigue-resistant (FR)-type MUs are generally similar but show weaker onion skin behaviors than FF-type MUs. Our results offer an explanation for the longstanding dichotomy regarding MU firing patterns, shedding light on the factors influencing the firing-recruitment schemes.NEW & NOTEWORTHY The literature reports two contrasting schemes, namely the onion skin and the afterhyperpolarization (AHP) regarding the relationship between motor units (MUs) firing rates and recruitment order. Previous studies have examined these schemes phenomenologically, imposing one scheme on the firing-recruitment relationship. Here, we used a high-fidelity computational model that prioritizes biological fidelity and heterogeneity to investigate motoneuron firing schemes without bias toward either scheme. Our objective findings offer an explanation for the longstanding dichotomy on MU firing patterns.


Asunto(s)
Modelos Neurológicos , Neuronas Motoras , Neuronas Motoras/fisiología , Potenciales de Acción/fisiología , Reclutamiento Neurofisiológico/fisiología , Humanos , Médula Espinal/fisiología , Animales , Simulación por Computador , Músculo Esquelético/fisiología
2.
Calcif Tissue Int ; 114(1): 9-23, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37603077

RESUMEN

Weakness, one of the key characteristics of sarcopenia, is a significant risk factor for functional limitations and disability in older adults. It has long been suspected that reductions in motor unit firing rates (MUFRs) are one of the mechanistic causes of age-related weakness. However, prior work has not investigated the extent to which MUFR is associated with clinically meaningful weakness in older adults. Forty-three community-dwelling older adults (mean: 75.4 ± 7.4 years; 46.5% female) and 24 young adults (mean: 22.0 ± 1.8 years; 58.3% female) performed torque matching tasks at varying submaximal intensities with their non-dominant leg extensors. Decomposed surface electromyographic recordings were used to quantify MUFRs from the vastus lateralis muscle. Computational modeling was subsequently used to independently predict how slowed MUFRs would negatively impact strength in older adults. Bivariate correlations between MUFRs and indices of lean mass, voluntary activation, and physical function/mobility were also assessed in older adults. Weak older adults (n = 14) exhibited an approximate 1.5 and 3 Hz reduction in MUFR relative to non-weak older adults (n = 29) at 50% and 80% MVC, respectively. Older adults also exhibited an approximate 3 Hz reduction in MUFR relative to young adults at 80% MVC only. Our model predicted that a 3 Hz reduction in MUFR results in a strength decrement of 11-26%. Additionally, significant correlations were found between slower MUFRs and poorer neuromuscular quality, voluntary activation, chair rise time performance, and stair climb power (r's = 0.31 to 0.43). These findings provide evidence that slowed MUFRs are mechanistically linked with clinically meaningful leg extensor weakness in older adults.


Asunto(s)
Fragilidad , Músculo Esquelético , Adulto Joven , Humanos , Femenino , Anciano , Masculino , Músculo Esquelético/fisiología , Pierna , Neuronas Motoras/fisiología , Factores de Riesgo , Fuerza Muscular/fisiología
3.
BMC Vet Res ; 20(1): 105, 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493097

RESUMEN

The aim of this study was to examine the effects of salt addition on the skin gene expression of Mucin, Antimicrobial peptides, cortisol, and glucose in Oreochromis niloticus after 5-hour transportation in water. Three groups were compared: Control, post-transport without salt (PT-S), and post-transport with 5 g salt-1(PT + S), with a stocking density of 28.6 gL-1, 20 fish for each experimental group. The results showed that the PT-S group had more significant changes in gene expression than the PT + S group, suggesting that salt alleviated the stress and immune responses of O. niloticus. The PT-S group had higher expression of mucin- 2(MUC + 2) (7.58 folds) and mucin-5AC (MUC5-AC) (6.29 folds) than the PT + S group (3.30 folds and 4.16 folds, respectively). The PT-S group also had lower expression of ß-defensin-1 (Dß1) (0.42 folds), ß-defensin-2 (Dß2) (0.29 folds), and Cath1 (0.16 folds) than the PT + S group (0.82 folds, 0.69 folds, and 0.75 folds, respectively). The skin morphology of the PT-S group revealed some white patches with no goblet cell openings, while the PT + S group had better preservation of skin features with some goblet cell openings and slight white patches. This study indicates that O. niloticus can benefit from sodium chloride during transportation, as it helps to reduce stress and inflammation, balance mineral levels, enhance health and immunity, and regulate mucous secretion.


Asunto(s)
Cíclidos , Enfermedades de los Peces , beta-Defensinas , Animales , Cloruro de Sodio , beta-Defensinas/genética , Agua , Mucinas , Alimentación Animal/análisis , Dieta
4.
BMC Vet Res ; 20(1): 55, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38350905

RESUMEN

Oreochromis niloticus (Nile tilapia) is a well-known economic fish species that can thrive under the right environmental circumstances. The transport of live fish, either for food or as companion animals, presents a big issue for animal welfare at the same time it is considered one of stressful conditions. Hence, the present study investigated the skin histopathological responses of O. niloticus that were attributed to stress and salt addition during transportation. Three experimental groups of O. niloticus the 1st is the control non-transported group (CG), the 2nd is transport in water without salt (PT-S) and the 3rd is transport in water containing 5gL- 1salt (PT + S), the last 2 groups were transported in 5 h transport model. Results indicate that the skin of PT-S fish showed a marked decrease in epidermal thickness, decreased number of goblet cells, and an increase in the sub-epidermal and dermal pigments with the presence of large edematous vacuoles. Fish skin from PT + S demonstrated mild hydropic swelling in epidermal cells with normal goblet (mucous) cells density, and more or less normal melanin pigment distribution in sub epidermis and on the dermis layers, however, dermis showed mild edematous spaces. Scanning microscopy of PT-S skin tissue showed few scratched white patches among normal regions that may represent a thickened surface with the decreased number of goblets cell opening, while the PT + S group showed moderate preservation of surface skin architectures with the presence of goblet (mucous) cells opening in spite of presence of slight thickened white patches. The estimated total lesion changes present in PT-S group showed a significant increase (P < 0.001) compared with the control (CG) group. On the other hand, PT + S showed significant (P < 0.001) improvement in the overall previously recorded changes compared with the PT-S group, and a non- significant change in the histological architectures compared with the control group. Our findings underlined the importance of skin and its mucous cover health during transportation. The use 5 gL- 1salt during O. niloticus transportation appears to preserve the surface skin features, and keep the goblet (mucous) cells open to the external surface, and may act as a deterrent for the release of mucus from goblet (mucous) cells in response to stress and lessen the stress of transportation.


Asunto(s)
Cíclidos , Enfermedades de los Peces , Animales , Piel/metabolismo , Epidermis
5.
Vet Pathol ; : 3009858241249108, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712876

RESUMEN

Novel goose parvovirus (NGPV) is continuously threatening the global duck industry, as it causes short beak and dwarfism syndrome among different duck breeds. In this study, we investigated the viral pathogenesis in the tongue of affected ducks, as a new approach for deeper understanding of the syndrome. Seventy-three, 14- to 60-day-old commercial Pekin ducks were clinically examined. Thirty tissue pools of intestine and tongue (15 per tissue) were submitted for molecular identification. Clinical signs in the examined ducks were suggestive of parvovirus infection. All examined ducks had short beaks. Necrotic, swollen, and congested protruding tongues were recorded in adult ducks (37/73, 51%). Tongue protrusion without any marked congestion or swelling was observed in 20-day-old ducklings (13/73, 18%), and no tongue protrusion was observed in 15-day-old ducklings (23/73, 32%). Microscopically, the protruding tongues of adult ducks showed necrosis of the superficial epithelial layer with vacuolar degeneration. Glossitis was present in the nonprotruding tongues of young ducks, which was characterized by multifocal lymphoplasmacytic aggregates and edema in the propria submucosa. Immunohistochemical examination displayed parvovirus immunolabeling, mainly in the tongue propria submucosa. Based on polymerase chain reaction, goose parvovirus was detected in 9 out of 15 tongue sample pools (60%). Next-generation sequencing confirmed the presence of a variant goose parvovirus that is globally named NGPV and closely related to Chinese NGPV isolates. Novel insights are being gained from the study of NGPV pathogenesis in the tongue based on molecular and immunohistochemical identification.

6.
Eur Heart J Suppl ; 25(Suppl H): H8-H12, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38046888

RESUMEN

Pacemaker therapy is the cornerstone in treatment of bradycardia and conduction disorders. Several diagnostic tools are utilized to diagnose and guide the physicians for appropriate management and accordingly proper utilization of pacemaker therapy. The current article is discussing the different diagnostics used for appropriate evaluation and diagnosis of bradyarrhythmias and the suggested solutions to improve bradycardia diagnosis and pacemaker therapy utilization in underpenetrated areas.

7.
J Acoust Soc Am ; 154(6): 3943-3954, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38147018

RESUMEN

Thermoacoustic refrigerators exploit the thermodynamic interaction between oscillating gas particles and a porous solid to generate a temperature gradient that provides a cooling effect. In this work, we present a resonator with dual enclosed driver end-caps and show that the temperature gradient across a ceramic thermoacoustic element placed in the cavity could be controlled by modifying the phase difference of the drivers, thus enabling precise control of the refrigeration capability via the temperature difference. Through deltaec simulation results, the response of the temperature gradient to various dynamic boundary conditions that alter the time-phasing and wave dynamics in the resonator are demonstrated. An experimental apparatus is constructed with two moving-coil speakers and a ceramic stack, which is shown to exhibit a temperature gradient along its length, based on the traveling-wave-like nature of the acoustic wave excited by the speakers. By adjusting the relative phase lag between the two speakers, the temperature gradient across the stack is made to increase, decrease, or flip sign. Finally, a desired temperature difference that changes in time is achieved. The results presented in this work represent a key conceptual advancement of thermoacoustic-based temperature control devices that can better serve in extreme environments and precision applications.

8.
J Neurophysiol ; 125(4): 1450-1467, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33689515

RESUMEN

Although slice recordings from spinal motoneurons (MNs) are being widely used, the effects of slicing on the measured MN electrical properties under normal and disease conditions have not been assessed. Using high-fidelity cell models of neonatal wild-type (WT) and superoxide dismutase-1 (SOD) cells, we examined the effects of slice thickness, soma position within the slice, and slice orientation to estimate the error induced in measured MN electrical properties from spinal slices. Our results show that most MN electrical properties are not adversely affected by slicing, except for cell time constant, cell capacitance, and Ca2+ persistent inward current (PIC), which all exhibited large errors, regardless of the slice condition. Among the examined factors, soma position within the slice appears to be the strongest factor in influencing the magnitude of error in measured MN electrical properties. Transverse slices appear to have the least impact on measured MN electrical properties. Surprisingly, and despite their anatomical enlargement, we found that G85R-SOD MNs experience similar error in their measured electrical properties to those of WT MNs, but their errors are more sensitive to the soma position within the slice than WT MNs. Unless in thick and symmetrical slices, slicing appears to reduce motoneuron type differences. Accordingly, slice studies should attempt to record from MNs at the slice center to avoid large and inconsistent errors in measured cell properties and have valid cell measurements' comparisons. Our results, therefore, offer information that would enhance the rigor of MN electrophysiological data measured from the slice preparation under normal and disease conditions.NEW & NOTEWORTHY Although slice recordings from motoneurons are being widely used, the effects of slicing on the measured motoneuron electrical properties under normal and disease conditions have not been assessed. Using high-fidelity cell models of neonatal WT and SOD cells, we examined the effects of slice thickness, soma position within the slice, and slice orientation. Our results offer information that enhances the rigor of MN electrophysiological data measured from the slice preparation under normal and disease conditions.


Asunto(s)
Fenómenos Electrofisiológicos/fisiología , Modelos Neurológicos , Neuronas Motoras/fisiología , Médula Espinal/fisiología , Esclerosis Amiotrófica Lateral , Animales , Ratones , Superóxido Dismutasa-1
9.
Mol Cell Biochem ; 476(9): 3433-3448, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33973131

RESUMEN

Amiodarone (AMD) is a widely used antiarrhythmic drug prescribed to treat cardiac tachyarrhythmias; however, AMD has been reported to provoke pulmonary fibrosis (PF) and hepatotoxicity. This study aimed to investigate the influence of alpha lipoic acid (ALA) on AMD-induced PF and hepatotoxicity in male Wistar rats. AMD administration resulted in elevated lung contents of hydroxyproline (Hyp), malondialdehyde (MDA), and increased serum levels of transforming growth factor beta-1 (TGF-ß1), interferon-γ (IFN-γ), alanine amino transaminase (ALT), aspartate amino transaminase (AST), total cholesterol (TC), and glucose. On the other side, lung content of glutathione reduced (GSH) and serum levels of total anti-oxidant capacity (TAC) were significantly decreased. Histopathologically, AMD caused PF, produced a mild hepatic injury, and increased expression of alpha smooth muscle actin (α-SMA). Treatment with ALA produced a significant reversal of the oxidative stress, fibrosis, and inflammation parameters with reductions in α-SMA expressions, leading to amelioration of histopathological lesions. ALA might provide supportive therapy in AMD-receiving cardiovascular patients.


Asunto(s)
Amiodarona/toxicidad , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Sustancias Protectoras/farmacología , Fibrosis Pulmonar/prevención & control , Ácido Tióctico/farmacología , Alanina Transaminasa/metabolismo , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocinas/metabolismo , Glutatión/metabolismo , Mediadores de Inflamación/metabolismo , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Ratas , Ratas Wistar , Vasodilatadores/toxicidad
10.
Saudi Pharm J ; 29(11): 1238-1249, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34819785

RESUMEN

This study aimed to develop propolis and tea tree oil nanoemulsion loaded with clindamycin hydrochloride to heal wound effectively. Nanoemulsion formulae were prepared and characterized by droplet size analysis, zeta potential, viscosity, ex-vivo permeation, and skin deposition. The optimal formula was evaluated in terms of morphology, cytotoxicity, and in-vitro wound healing assay. Also, the efficacy of the optimal formula was evaluated by in-vivo wound healing and histopathological studies. The optimal formula (F3) was composed of 9% tea tree oil and 0.4% propolis extracts with mean droplet size 19.42 ± 1.7 nm, zeta potential value -24.5 ± 0.2 mV, and viscosity 69.4 ± 1.8 mP. Furthermore, the optimal formula showed the highest skin deposition value 550.00 ± 4.9 µg/cm2 compared to other formulae. The TEM micrograph of the optimal formula showed that the nanoemulsion droplet has an almost spherical shape. Also, the optimal formula did not show noticeable toxicity to the human skin fibroblast cells. The in-vitro and in-vivo wound healing assay showed unexpected results that the un-loaded drug nanoemulsion formula had a comparable wound healing efficacy to the drug-loaded nanoemulsion formula. These results were confirmed with histopathological studies. Our results showed that the propolis and tea tree oil nanoemulsion, whether loaded or unloaded with an antibiotic, is an efficient local therapy for wound healing.

11.
J Neurophysiol ; 124(4): 1285-1307, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32937080

RESUMEN

Persistent inward currents are important to motoneuron excitability and firing behaviors and also have been implicated in excitotoxicity. In particular, L-type Ca2+ channels, usually located on motoneuron dendrites, play a primary role in amplification of synaptic inputs. However, recent experimental findings on L-type Ca2+ channel behaviors challenge some fundamental assumptions that have been used in interpreting experimental and computational modeling data. Thus, the objectives of this study were to incorporate recent experimental data into an updated, high-fidelity computational model in order to explain apparent inconsistencies and to better elucidate the spatial distributions, expression patterns, and functional roles of L-type Ca2+ and SKL channels. Specifically, the updated model incorporated asymmetric channel activation/deactivation kinetics, depolarization-dependent facilitation, randomness in channel gating, and coactivation of SKL channels. Our simulation results suggest that L-type Ca2+ and SKL channels colocalize primarily on distal dendrites of motoneurons in a punctate expression. Also, punctate expression, as opposed to a homogeneous expression, provides high synaptic current amplification, limits bistability and firing rates, and robustly regulates the Ca2+ persistent inward current, thereby reducing risk of excitotoxicity. The hysteresis and bistability observed experimentally in current-voltage and frequency-current relationships result from the L-type Ca2+ channels' distal location and intrinsic warm-up. Accordingly, our results indicate that punctate expression of L-type Ca2+ and SKL channels is a potent mechanism for regulating excitability, which would provide a strong neuroprotective effect. Our results could provide broader insights into the functional significance of warm-up and punctate expression of ion channels to regulation of cell excitability.NEW & NOTEWORTHY Recent experimental findings on L-type Ca2+ channels challenge fundamental assumptions used in interpreting experimental and computational modeling data. Here, we incorporated recent experimental data into an updated, high-fidelity computational model to explain apparent inconsistencies and better elucidate the distributions, expression patterns, and functional roles of L-type Ca2+ and SKL channels. Our results indicate that punctate expression of L-type Ca2+ and SKL channels is a potent mechanism for regulating motoneuron excitability, providing a strong neuroprotective effect.


Asunto(s)
Canales de Calcio Tipo L/metabolismo , Dendritas/metabolismo , Modelos Neurológicos , Neuronas Motoras/metabolismo , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/metabolismo , Médula Espinal/citología , Potenciales de Acción , Animales , Canales de Calcio Tipo L/genética , Gatos , Simulación por Computador , Dendritas/fisiología , Neuronas Motoras/fisiología , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/genética
12.
Acta Vet Hung ; 68(2): 221-230, 2020 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-32894731

RESUMEN

Newcastle disease virus (NDV) remains a constant threat to the poultry industry even with intensive vaccination programmes. In the present study, 40 samples were collected from farms showing high mortalities in some Egyptian governorates between 2016 and 2018. Tracheal samples were collected for virus isolation and confirmed by real-time RT-PCR. Molecular characterisation was performed by sequencing, followed by phylogenetic analysis of the novel sequences. Histopathological and immunohistochemical examinations were performed on different organs from NDV-infected broilers. The phylogenetic analysis revealed that the NDV isolates from different areas of Egypt were genetically closely related and all belonged to genotype VII. The histopathological hallmarks included haemorrhagic tracheitis, interstitial pneumonia with syncytia formation, haemorrhagic proventriculitis, necrotising pancreatitis, pan-lymphoid depletion, non-suppurative encephalitis and nephritis. Immunological detection of NDV antigen clarified the widespread presence of viral antigen in different organs with severe lesions. The present study confirmed that a virulent NDV of genotype VII became the predominant strain, causing severe outbreaks in poultry farms in Egypt. The presence of viral antigen in different organs indicates the pantropic nature of the virus. Immunohistochemistry was a very useful diagnostic tool for the detection of NDV antigen.


Asunto(s)
Pollos , Genotipo , Enfermedad de Newcastle/virología , Virus de la Enfermedad de Newcastle/genética , Enfermedades de las Aves de Corral/virología , Animales , Egipto
13.
Acta Vet Scand ; 66(1): 27, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956671

RESUMEN

BACKGROUND: Heterakis gallinarum (H. gallinarum) is a common poultry parasite that can be found in the ceca of many gallinaceous bird species, causing minor pathology and reduced weight gain. Most infections go unnoticed in commercial flocks due to the dependence on fecal egg counts, which are prone to false-negative diagnoses. Furthermore, there is a lack of research on gastrointestinal nematodes that use molecular identification methods, which could be essential for rapid diagnosis and developing efficient control approaches. As a result, the study aimed to look at the cause of mortality in layer chickens induced by H. gallinarum in Egyptian poultry farms using morphological, ultrastructural, and molecular characterization. Histopathological, immunohistochemical, and cell-mediated immune responses from damaged cecal tissues were also examined. RESULTS: Seventy bird samples from ten-layer flocks of different breeds (Native, white, and brown layers) suffering from diarrhea, decreased egg output, and emaciation were collected. Cecal samples were collected from affected and non-affected birds and were examined for parasitic diseases using light and a scanning electron microscope. The mitochondrial cytochrome oxidase 1 (COX1) gene was used to characterize H. gallinarum. Our results showed that the collected nematodal worms were identified as H. gallinarum (male and female), further confirmed by COX1 gene amplification and sequence alignment. Gene expression analysis of the inflammatory markers in infected tissues showed a significant up-regulation of IL-2, IFN-γ, TLR-4, and IL-1ß and a significant down-regulation of the anti-inflammatory IL-10. The mRNA level of the apoptotic cas-3 revealed apoptotic activity among the H. gallinarum samples compared to the control group. CONCLUSIONS: Our results implemented the use of molecular methods for the diagnosis of Heterakis, and this is the first report showing the tissue immune response following infection in layers: upregulation of IL-1ß, IFN-γ, Il-2, and TLR-4, while down-regulation of anti-inflammatory IL-10 in cecal tissue, Cas-3 apoptotic activity and Nuclear factor-κB (NF-κB)activity with immunophenotyping of T-cells in Heterakis infected tissue.


Asunto(s)
Ciego , Pollos , Enfermedades de las Aves de Corral , Tiflitis , Animales , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/patología , Tiflitis/veterinaria , Tiflitis/parasitología , Tiflitis/patología , Ciego/parasitología , Ciego/patología , Femenino , Inmunidad Celular , Infecciones por Ascaridida/veterinaria , Infecciones por Ascaridida/parasitología , Ascaridoidea , Egipto
14.
Int J Pharm ; 653: 123876, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38331331

RESUMEN

Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease that severely affects joint function. Despite the variability of treatment protocols, all of them are associated with severe side effects that compromise patient compliance. The main aim of the current study is to prepare localized effective RA treatment with reduced side effects by combining nanoencapsulation, photodynamic therapy (PDT) and hollow microneedles (Ho-MNs) to maximize the pharmacological effects of hypericin (HYP). To attain this, HYP-loaded emulsomes (EMLs) were prepared, characterized and administered through intradermal injection using AdminPen™ Ho-MNs combined with PDT in rats with an adjuvant-induced RA model. The prepared EMLs had a spherical shape and particle size was about 93.46 nm with an absolute entrapment efficiency. Moreover, confocal imaging indicated the interesting capability of Ho-MNs to deposit the HYP EMLs to a depth reaching 1560 µm into the subcutaneous tissue. In vivo, study results demonstrated that the group treated with HYP EMLs through Ho-MNs combined with PDT had no significant differences in joint diameter, TNF-α, IL1, HO-1, NRF2 and SD levels compared with the negative control group. Similarly, rats treated with the combination of HYP EMLs, Ho-MNs and PDT showed superior joint healing efficacy compared with the groups treated with HYP EMLs in dark, HYP ointment or HYP in microneedles in histopathological examination. These findings highlight the promising potential of photoactivated HYP EMLs when combined with Ho-MNs technology for RA management. The presented therapeutic EMLs-MNs platform could serve as a powerful game-changer in the development of future localized RA treatments.


Asunto(s)
Artritis Reumatoide , Perileno/análogos & derivados , Fotoquimioterapia , Humanos , Ratas , Animales , Fotoquimioterapia/métodos , Antracenos , Artritis Reumatoide/tratamiento farmacológico , Fármacos Fotosensibilizantes
15.
ACS Omega ; 9(12): 14198-14209, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38559915

RESUMEN

In this work, a novel, green, and atom-efficient method for the synthesis of tetrahydro-ß-carboline derivatives using electrochemistry (EC) in deep eutectic solvents (DESs) was reported. The EC reaction conditions were optimized to achieve the highest yield. The experimental design was also optimized to perform the reaction in a two-step, one-pot reaction, thereby the time, workup procedure, and solvents needed were all reduced. The new approach achieved our strategy as EC served to decrease the time of reaction, eliminate the use of hazardous catalysts, and lower the energy required for the synthesis of the targeted compounds. On the other side, DESs were used as catalysts, in situ electrolytes, and noninflammable green solvents. The scope of the reaction was investigated using different aromatic aldehydes. Finally, the scalability of the reaction was investigated using a gram-scale reaction that afforded the product in an excellent yield.

16.
Sci Rep ; 14(1): 18069, 2024 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103392

RESUMEN

Worldwide, particularly in developing nations, helminth infections are the leading causes of livestock illness and mortality. Parascaris (P.) equorum, a parasitic worm from the Ascarididae family, significantly impacts the production, health, and working performance of equines. This study aimed to investigate the impact of intraperitoneal sensitization of P. equorum on the immune system, oxidative stress, and histology in Wistar rats. After acclimatization for 7 days, we divided the rats into five groups, each consisting of six rats. Group I, serving as the control, was administered distilled water, followed by groups II (day 7), III (day 14), IV (day 21), and V (day 33). The rats were euthanized every day mentioned (Days 7-33). On day 0, a dosage of 1ml/100 gm rat (containing 500 µg/ml protein content) emulsified crude antigen extract with an incomplete Freund's adjuvant (1:1 volume), followed by a second dose of the same antigen concentration on day 7. To assess the allergenicity of this nematode, we measured a whole blood profile, serum levels of IFN-γ, IL-5, IL-10, IL-13, and IL-33, total immunoglobulins IgE and IgG, and oxidative stress markers. Also, we examined histological changes in the liver, kidney, and spleen. The results showed that values of total leukocyte count, granulocytes, monocytes, and lymphocytes were significantly (P < 0.05) increased on day 14 post-infection relative to other days of investigation. It was found that the levels of total immunoglobulins (IgE and IgG) and cytokines (INF-γ, IL-5, IL-13, and IL-33) on days 14 and 21 were significantly higher than in the control group. At all periods of the experiment, the injected group exhibited significantly higher concentrations of MDA and NO compared to the control group (P < 0.05). Conversely, GSH and CAT levels (P < 0.05) dropped significantly on days 7, 14, and 21. Different rat tissues showed alterations. Ultimately, this study described the detrimental effects of P. equorum crude antigen administration on the immune system, oxidative states, and histological changes of Wistar rats at various intervals.


Asunto(s)
Antígenos Helmínticos , Estrés Oxidativo , Ratas Wistar , Animales , Ratas , Antígenos Helmínticos/inmunología , Ascaridoidea/inmunología , Citocinas/metabolismo , Masculino
18.
J Parasit Dis ; 48(1): 14-24, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38440749

RESUMEN

Complications of parasite infections, especially kidney disease, have been linked to poorer outcomes. Acute kidney damage, glomerulonephritis, and tubular dysfunction are the most prevalent renal consequences of Parascaris equorum infection. The purpose of this study was to determine the pharmacological effects of green-produced zinc oxide nanoparticles (ZnO NPs) on P. equorum infection in male Wistar rats. Thirty-six male rats were divided into two groups of 18 each: infected and non-infected. Both groups were separated into three subgroups, each of which received distilled water, 30 mg/kg ZnO NPs, and 60 mg/kg ZnO NPs. After 10 days of ZnO NPs administration, four larvae per gram of kidney tissue were present in the untreated infected group. While, no larvae were present in ZnO NPs (30 mg/kg) treated group, and one larva/g.tissue was present in ZnO NPs (60 mg/kg) treated group compared to untreated infected animals. P. equorum infected rats had increased kidney biomarkers (creatinine, urea, uric acid), malondialdehyde, and nitric oxide, with a significant decrease in their antioxidant systems. On the other hand, infected treated rats with green-produced zinc oxide nanoparticles had a substantial drop in creatinine, urea, uric acid, malondialdehyde, and nitric oxide, as well as a significant rise in their antioxidant systems. P. equorum infection in rats caused severe degenerative and necrotic renal tissues. On the other hand, there were no detectable histopathological alterations in rats treated with ZnO NPs (30, 60 mg/kg) as compared to the infected untreated animals. When compared to infected untreated mice, immunohistochemical examination of nuclear factor-kappa B showed a significant decrease during treatment with ZnO NPs (30, 60 mg/kg). Green-produced zinc oxide nanoparticles are a viable therapeutic strategy for Parascaris equorum infection due to their potent anthelmintic activity, including a significant decrease in larval burden in infected treated rats.

19.
Poult Sci ; 103(1): 103227, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38041891

RESUMEN

The chicken business faces substantial economic losses due to the risk of parasitic coinfection. Because the current study aimed to investigate enteric parasitic coinfections problems among the suspected examined chicken farms, samples were collected during the field investigation from suspected freshly dead birds, clinically diseased, apparently healthy, and litter samples for further laboratory parasitological, histopathological, and immunological examinations. Variable mortalities with various clinical indicators, such as ruffled feathers, weight loss, diarrhea of various colors, and a decline in egg production, occurred on the farms under investigation. In addition, the treatment protocols of each of the farms that were evaluated were documented and the m-RNA levels of some cytokines and apoptotic genes among the infected poultry have been assessed. The prevalence rate of parasitic coinfection in the current study was found to be 8/120 (6.66%). Parasitological analysis of the samples revealed that they belonged to distinct species of Eimeria, cestodes, and Ascaridia galli. When deposited, A. galli eggs were nonembryonated and ellipsoidal, but cestodes eggs possessed a thin, translucent membrane that was subspherical. Eimeria spp. oocysts in layer chickens were identified as Eimeria acervulina and Eimeria maxima in broiler chickens. Our findings proved that coinfection significantly upregulated the IL-1ß, BAX, and Cas-3 genes. Conversely, the IL-10, BCL-2, and AKT mRNA levels were downregulated, indicating that nematode triggered apoptosis. The existence of parasite coinfection was verified by histological investigation of the various intestinal segments obtained from affected flocks. A. galli and cestodes obstructed the intestinal lumen, causing different histological alternations in the intestinal mucosa. Additionally, the lamina propria revealed different developmental stages of Eimeria spp. It was determined that parasite coinfection poses a significant risk to the poultry industry. It was recommended that stringent sanitary measures management methods, together with appropriate treatment and preventative procedures, be employed in order to resolve such issues.


Asunto(s)
Coccidiosis , Coinfección , Eimeria , Parásitos , Enfermedades de las Aves de Corral , Animales , Coccidiosis/epidemiología , Coccidiosis/veterinaria , Coccidiosis/parasitología , Pollos/parasitología , Coinfección/epidemiología , Coinfección/veterinaria , Enfermedades de las Aves de Corral/parasitología , Óvulo , Eimeria/genética
20.
Health Inf Sci Syst ; 12(1): 36, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38868156

RESUMEN

Ocular diseases pose significant challenges in timely diagnosis and effective treatment. Deep learning has emerged as a promising technique in medical image analysis, offering potential solutions for accurately detecting and classifying ocular diseases. In this research, we propose Ocular Net, a novel deep learning model for detecting and classifying ocular diseases, including Cataracts, Diabetic, Uveitis, and Glaucoma, using a large dataset of ocular images. The study utilized an image dataset comprising 6200 images of both eyes of patients. Specifically, 70% of these images (4000 images) were allocated for model training, while the remaining 30% (2200 images) were designated for testing purposes. The dataset contains images of five categories that include four diseases, and one normal category. The proposed model uses transfer learning, average pooling layers, Clipped Relu, Leaky Relu and various other layers to accurately detect the ocular diseases from images. Our approach involves training a novel Ocular Net model on diverse ocular images and evaluating its accuracy and performance metrics for disease detection. We also employ data augmentation techniques to improve model performance and mitigate overfitting. The proposed model is tested on different training and testing ratios with varied parameters. Additionally, we compare the performance of the Ocular Net with previous methods based on various evaluation parameters, assessing its potential for enhancing the accuracy and efficiency of ocular disease diagnosis. The results demonstrate that Ocular Net achieves 98.89% accuracy and 0.12% loss value in detecting and classifying ocular diseases by outperforming existing methods.

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