How to create an experimental diabetes mellitus model?

Diabetes is a metabolic disorder characterized by chronic hyperglycemia. Early treatment is very important in terms of preventing diabetes-related late complications with high treatment costs and increasing the patient’s quality of life. In addition to investigating the pathophysiology of the disease studied, animal experiments pave the way for new approaches in treatments. Although there are many methods that can be used when creating a diabetes model, induction of diabetes with alloxan and streptozotocin are the most preferred ones. The aim of this article is to review the available information on diabetes-related methods, common problems and solutions, with known mechanisms of action, dose and time-determined methods

Effects of vincamine on testicular dysfunction in alloxan-induced diabetic male rats

Background: Diabetes mellitus (DM) is frequently linked with problems of several organ systems, including retinopathy, neuropathy, and nephropathy. Additionally, patients have changes in sexual functioning, such as decreased libido and fertility. Vincamine, a monoterpenoid indole alkaloid, has hypoglycemic and antioxidant effects. Objectives: This research assessed the impact of vincamine on testicular dysfunction in alloxan-induced male rats by measuring fasting blood glucose, oxidative stress, seminal analysis, and histological examination of the testis. Methods: Wister-albino male rats were randomized into the following groups at random: Untreated-healthy, untreated-DM, vincamine-treated (20 mg/kg) DM, vincamine-treated (40 mg/kg) DM, and clomiphene-treated DM (5 mg/kg). On day 14, rats were sacrificed, and semen/blood samples were collected. Sperm count, motility, and morphological abnormalities were noted by microscopic examination. The testis was examined histopathologically and assessed using Johnsen’s score. Results: Compared with the untreated diabetic group, a dosage of 40 mg/kg vincamine generate a significant reduction in fasting blood sugar (FBG). Compared with the untreated diabetic group, the vincamine-treated rats produced greater plasma testosterone levels and Johnsen scores. In the vincamine 20 mg/kg group, sperm concentration was higher than in the vincamine 40 mg/kg group. Conclusions: It is possible that vincamine has a potential preventive effect against diabetes-related reproductive problems attributable to its antioxidant activity and capacity to restore testicular steroidogenesis

Wound physiology and experimental wound models: Traditional review

Yara, vücuda gelebilecek bir yaralanma sonucu cildin epidermisinde hasar oluşması ve derinin normal anatomisinin ve fonksiyonlarının bozulması olarak tanımlanır. Yara iyileşmesi, kazayla veya kasıtlı olarak meydana gelen travma sonrası derinin bütünlüğünü korumak için önemli bir fizyolojik süreçtir. Normal yara iyileşmesi, hemostaz/inflamatuar faz, inflamasyon, proliferatif faz ve yeniden şekillenme fazı dâhil olmak üzere birbirini takip eden ve üst üste binen 4 fazı içerir. Yara iyileşmesi; yaş, eşlik eden hastalık, beslenme ve hijyen gibi birçok faktör tarafından etkilenmektedir. Aşırı yara iyileşmesi (hipertrofik skar ve keloid) veya kronik yara (ülser), bozulmuş fizyolojik yara iyileşme süreçlerinin göstergesidir. Yaraların temelde akut/kronik olarak ayrılmasının yanında, oluştuğu bölge (ağız, göz, deri vb.) ve oluşumuna göre (travmaya bağlı yara, diyabetik yara ve yanık yaraları) sınıflandırılması, bakımı ve tedavisi açısından farklılıklar oluşturmaktadır. Genel olarak topikal antiseptikler ile yapılan geleneksel yara bakımının yanında günümüzde otogreftler, allogreftler, kültürlü epitelyal otogreftler ve biyouyumlu ve biyobozunur polimerlere dayalı yara pansumanları gibi tedavi seçenekleri de bulunmaktadır. Deneysel yara modelleri, terapötik potansiyele sahip yeni ajanları test etmek, doku onarım mekanizmasının patogenezini incelemek ve yeni biyobelirteçleri saptamak için gereklidir. İn silico, in vitro ve in vivo dâhil olmak üzere yara iyileşme sürecini incelemek için çeşitli modeller kullanılmıştır. Bunun yanında, hiçbir deneysel yara modeli fizyolojik yara iyileşmesini tam olarak temsil etmediği için farklı modelleri içeren uygun bir kombinasyon kullanılmalıdır. Bu derlemede; yara tipleri, yara iyileşmesi, in vitro ve in vivo deneysel yara modelleri tartışılmaktadır.Wound is defined as damage to the epidermis of the skin and disruption of the normal anatomy and functions of the skin as a result of an injury to the body. Wound healing is an important physiological process to preserve the integrity of the skin after accidental or intentional trauma. Normal wound healing includes four consecutive and overlapping phases, including the hemostasis/inflammatory phase, the inflammation, the proliferative phase, and the remodeling phase. Wound healing; it is affected by many factors such as age, concomitant disease, nutrition and hygiene. Excessive wound healing (hypertrophic scar and keloid) or chronic wound (ulcer) is indicative of impaired physiological wound healing processes. In addition to the acute/chronic division of wounds, the classification according to the region (mouth, eye, skin etc.) and formation (traumatic wound, diabetic wound and burn wounds) creates differences in terms of care and treatment. In addition to traditional wound care with topical antiseptics in general, treatment options such as autografts, allografts, cultured epithelial autografts and wound dressings based on biocompatible and biodegradable polymers are now available. Experimental wound models are required to test new agents with therapeutic potential, to study the pathogenesis of tissue repair mechanism, and to detect new biomarkers. Various models have been used to study the wound healing process, including in silico, in vitro, and in vivo. In addition, an appropriate combination of different models should be used, as no experimental wound model is fully representative of physiological wound healing. In this review, wound types, wound healing, in vitro and in vivo experimental wound models are discussed

Protein and gene delivery systems for neurodegenerative disorders: Where do we stand today?

It has been estimated that every year, millions of people are affected by neurodegenerative disorders, which complicate their lives and their caregivers’ lives. To date, there has not been an approved pharmacological approach to provide the complete treatment of neurodegenerative disorders. The only available drugs may only relieve the symptoms or slow down the progression of the disease. The absence of any treatment is quite rational given that neurodegeneration occurs by the progressive loss of the function or structure of the nerve cells of the brain or the peripheral nervous system, which eventually leads to their death either by apoptosis or necrotic cell death. According to a recent study, even though adult brain cells are injured, they can revert to an embryonic state, which may help to restore their function. These interesting findings might open a new path for the development of more efficient therapeutic strategies to combat devastating neurodegenerative disorders. Gene and protein therapies have emerged as a rapidly growing field for various disorders, especially neurodegenerative diseases. Despite these promising therapies, the complete treatment of neurodegenerative disorders has not yet been achieved. Therefore, the aim of this review is to address the most up-to-date data for neurodegenerative diseases, but most importantly, to summarize the available delivery systems incorporating proteins, peptides, and genes that can potentially target such diseases and pass into the blood–brain barrier. The authors highlight the advancements, at present, on delivery based on the carrier, i.e., lipid, polymeric, and inorganic, as well as the recent studies on radiopharmaceutical theranostics

Investigation of the effects of vincamine on spermatogenesis in an alloxan-induced diabetic rat model

Diabetes mellitus sıklıkla retinopati, nöropati ve nefropati dahil olmak üzere çeşitli organ sistemlerinin sorunlarıyla bağlantılıdır. Ek olarak, hastaların cinsel işlevlerinde libido ve doğurganlıkta azalma gibi değişiklikler olur. Bir monoterpenoid indol alkaloid olan vinkamin, hipoglisemik ve antioksidan etkilere sahiptir. Bu araştırmanın amacı vinkaminin alloksan ile indüklenen erkek sıçanlarda testis disfonksiyonu üzerindeki etkisini, açlık kan şekeri, oksidatif stres, seminal analiz ve testisin histolojik incelemesini yaparak değerlendirmektir. 40 adet sıçanlar (n=8) olacak şekilde); sağlıklı kontrol, diyabetik kontrol, vinkamin (20mg/kg), vinkamin (40mg/kg) ve klomifen (5mg/kg) uygulanan diyabetik sıçanlar olmak üzere beş gruba ayrıldı. 14. günde, sakrifikasyon sonrası semen/kan örnekleri toplandı. Mikroskobik inceleme ile sperm sayısı, motilitesi ve morfolojisi araştırıldı. Testis, histopatolojik olarak incelenip Johnsen skoru kullanılarak değerlendirildi. 40 mg/kg VK grubunda, DM-kontrol grubuna kıyasla AKŞ'de belirgin bir azalma tespit edildi ve VK gruplarında doza bağlı olarak antioksidan etki gözlendi. VK gruplarında DM- kontrol grubuna kıyasla daha yüksek plazma testosteron seviyesi ve Johnsen skorları elde edildi. VK 20/mg/kg (p<0,01) grubunda sperm konsantrasyonunun VK 40 mg/kg (p<0,001) grubuna göre daha yüksek olduğu saptandı Sonuç olarak, diyabetle ilişkili üreme sorunlarına karşı vinkaminin, antioksidan aktivitesine ve testiküler steroidogenezi yeniden oluşturma kapasitesine atfedilebilecek potansiyel bir önleyici etkiye sahip olduğu söylenebilir.Diabetes mellitus is frequently linked with problems of several organ systems, including retinopathy, neuropathy, and nephropathy. Additionally, patients have changes in sexual functioning, such as decreased libido and fertility. Vincamine, a monoterpenoid indole alkaloid, has hypoglycemic and antioxidant effects. This research assessed the impact of vincamine on testicular dysfunction in alloxan-induced male rats by measuring fasting blood glucose, oxidative stress, seminal analysis, and histological examination of the testis. Rats were randomly divided into following groups (n=8); healthy control, diabetes control, vincamine-treated (20mg/kg) diabetes, vincamine-treated (40mg/kg) diabetes, and clomiphene-treated diabetics (5mg/kg) groups. On day 14, rats were sacrificed, and semen/blood samples collected. Sperm count, motility, morphological abnormalities were noted by microscopic examination. The testis was examined histopathologically and assessed using Johnsen's score. The dose of 40mg/kg vincamine resulted in a marked reduction in FBG as compared to diabetic control group. Additionally, the vincamine groups demonstrated dose- dependent antioxidant action. The vincamine-treated rats had higher plasma testosterone levels and Johnsen scores compared to the diabetic control animals. In vincamine 20mg/kg group, sperm concentration was higher than vincamine 40mg/kg group. As a result, it is possible that vincamine has a potential preventive effect against diabetes-related reproductive problems, which might be attributed to its antioxidant activity and capacity to restore testicular steroidogenesis

Effect of glabridin on microvascular permeability of plasma proteins induced by carrageenan

In present study, investigate the anti-inflammatory effects of glabridin (GLA) in the carrageenan-induced paw edema test of rats. Inflammation is an answer to the body's immune response to various stimuli such as physical trauma, various antigens chemicals, microorganisms radiation- damaged tissues. The cause of this edema is the increase of vascular permeability. an increase in local blood flow as well as the penetration of neutrophils and macrophages into the inflamed tissue. The current study aimed to determine the mechanism of microvascular leakage on carrageenan (CAR)-induced paw. edema of GLA. Therefore 10, 20 and 40 mg/kg doses of GLA were given intraperitoneal 3 days before intraplantar administration of CAR by using Evans blue (EB) method and by measuring paw thickness with electronic digital calipers. As a result, GLA inhibited both edema and microvascular leak. The results of our study suggest that pretreat-GLA to CAR -induced paw edema of rats via anti-inflammatory potential through inhibition of parameters such as microvascular escape and anti-edematous effect. These findings may be a new treatment of inflammation by anti-protein leakage of GLA

Extracto de raíz de Glycyrrhiza glabraatenúa la nocicepción en modelos experimentales de dolor: El rolde los canales BKCa

The aim of this study was to evaluate the functional interaction of Glycyrrhiza glabra root extract (GGRE) on the large conductance Ca2+-activated K+ (BKCa) channels expressed in the peripheral nervous system by using nociception and inflammation models in rodents in vivo. Besides toxicity studies and open field tests, nociception and inflammation tests were performed on rodents. Different doses of GGRE were given orally to rats and mice. Naloxone, indomethacin, morphine, NS1619 and iberiotoxin (IbTX) were administered. GGRE had both anti-nociceptive and anti-inflammatory activity in rats and mice. GGRE exhibited an analgesic effect by decreasing the time-course of the pain threshold or reaction time in some nociceptive tests. Furthermore, GGRE reduced level of pro-inflammatory cytokines, including TNF-alpha and IL-1 beta. As a conclusion, GGRE can alleviate the pain sensation of the afferent nerves and can reduce inflammation and associated pain by activating BKCa channels and reducing the levels of TNF-alpha, IL1 beta.Resumen:El objetivo de este estudio fue evaluar la interacción funcional del extracto de raíz de Glycyrrhiza glabra(GGRE) en los canales de K+(BKCa) activados por Ca2+de gran conductancia expresados en el sistema nervioso periférico mediante el uso de modelos de nocicepción e inflamación en roedores in vivo. Además de los estudios de toxicidad y las pruebas de campo abierto, se realizaron pruebas de nocicepción e inflamación en roedores. Se administraron por vía oral diferentes dosis de GGRE a ratas y ratones. Se administraron naloxona, indometacina, morfina, NS1619 e iberiotoxina (IbTX). GGRE tenía actividad tanto antinociceptiva como antiinflamatoria en ratas y ratones. GGRE mostró un efecto analgésico al disminuir la evolución temporal del umbral del dolor o el tiempo de reacción en algunas pruebas nociceptivas. Además, GGRE redujo el nivel de citocinas proinflamatorias, incluidas TNF-α e IL-1β. Como conclusión, GGRE puede aliviar la sensación de dolor de los nervios aferentes y puede reducir la inflamación y el dolor asociado activando los canales BKCa y reduciendo los niveles de TNF-α, IL1β

Phytochemical compounds loaded to nanocarriers as potential therapeutic substances for alzheimer’s disease-could they be effective?

Alzheimer's disease accounts for a high percentage of dementia cases in elderly individuals. This type of brain disease is caused by damage to the brain cells affecting the ability of the patients to communicate, as well as their thinking, behavior, and feelings. Although numerous research laboratories focus on advancements in treating Alzheimer's disease, the currently approved pharmacological approaches seem to only alleviate the symptoms. Consequently, there is an urgent need for alternative pharmacological options that can prevent the progressive impairment of neurons. Natural substances were used in ancient times to treat various disorders given their biological activities such as antioxidant, anti-inflammatory, and antiapoptotic properties. Besides, their cost-effectiveness and accessibility to anyone who needs them are their most significant characteristics. Therefore, the possible use of phytochemical compounds for the possible management or even prevention of Alzheimer's disease is currently under investigation. This review article summarizes the present status of Alzheimer's disease diagnosis and underlying mechanisms, the potential phytochemicals and their carriers, along with future perspectives. In the future, natural substances can play a role as an adjunct therapy for neurodegenerative forms of dementia, such as Alzheimer's disease

Phytochemical compounds loaded to nanocarriers as potential therapeutic substances for alzheimer’s disease-could they be effective?

Alzheimer's disease accounts for a high percentage of dementia cases in elderly individuals. This type of brain disease is caused by damage to the brain cells affecting the ability of the patients to communicate, as well as their thinking, behavior, and feelings. Although numerous research laboratories focus on advancements in treating Alzheimer's disease, the currently approved pharmacological approaches seem to only alleviate the symptoms. Consequently, there is an urgent need for alternative pharmacological options that can prevent the progressive impairment of neurons. Natural substances were used in ancient times to treat various disorders given their biological activities such as antioxidant, anti-inflammatory, and antiapoptotic properties. Besides, their cost-effectiveness and accessibility to anyone who needs them are their most significant characteristics. Therefore, the possible use of phytochemical compounds for the possible management or even prevention of Alzheimer's disease is currently under investigation. This review article summarizes the present status of Alzheimer's disease diagnosis and underlying mechanisms, the potential phytochemicals and their carriers, along with future perspectives. In the future, natural substances can play a role as an adjunct therapy for neurodegenerative forms of dementia, such as Alzheimer's disease