scholarly journals Triumeq Increases Excitability of Pyramidal Neurons in the Medial Prefrontal Cortex by Facilitating Voltage-Gated Ca2+ Channel Function

2021 ◽  
Vol 11 ◽  
Author(s):  
Lihua Chen ◽  
Lena Al-Harthi ◽  
Xiu-Ti Hu
Keyword(s):  
Prefrontal Cortex ◽  
Side Effects ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Voltage Gated ◽  
Hiv Aids

Combination antiretroviral therapy (cART) suppresses HIV-1 replication, improves immune function, and prolongs the life of people living with HIV (PLWH). However, cART also induces neurotoxicity that could complicate HIV-induced neurodegeneration while reduce its therapeutic efficacy in treating HIV/AIDS. Triumeq is a first-line cART regimen, which is co-formulated by three antiretroviral drugs (ARVs), lamivudine (3TC), abcavir (ABC), and dolutegravir (DTG). Little is known about potential side effects of ARVs on the brain (including those co-formulating Triumeq), and their mechanisms impacting neuronal activity. We assessed acute (in vitro) and chronic (in vivo) effects of Triumeq and co-formulating ARVs on pyramidal neurons in rat brain slices containing the medial prefrontal cortex (mPFC) using patch-clamp recording approaches. We found that acute Triumeq or 3TC in vitro significantly increased firing of mPFC neurons in a concentration- and time-dependent manner. This neuronal hyperactivity was associated with enhanced Ca2+ influx through voltage-gated Ca2+ channels (VGCCs). Additionally, chronic treatment with Triumeq in vivo for 4 weeks (4 wks) also significantly increased firing and Ca2+ influx via VGCCs in mPFC neurons, which was not shown after 2 wks treatment. Such mPFC neuronal hyperexcitability was not found after 4 weeks treatments of individual ARVs. Further, chronic Triumeq exposure in vivo significantly enhanced mRNA expression of low voltage-activated (LVA) L-type Ca2+ channels (Cav1.3 L-channels), while changes in high voltage-activated (HVA) Cav1.2 L-channels were not observed. Collectively, these novel findings demonstrate that chronic cART induces hyperexcitability of mPFC pyramidal neurons by abnormally promoting VGCC overactivation/overexpression of VGCCs (including, but may not limited to, LVA-Cav1.3 L-channels), which could complicate HIV-induced neurotoxicity, and ultimately may contribute to HIV-associated neurocognitive disorders (HAND) in PLWH. Determining additional target(s) of cART in mPFC pyramidal neurons may help to improve the therapeutic strategies by minimizing the side effects of cART for treating HIV/AIDS.

scholarly journals Contributions of the lay workers in providing home-based treatment adherence support to patients with advanced HIV/AIDS disease in low-income settings: Lessons learned from the field in Tanzania and Zambia

2020 ◽  
Vol 21 (2) ◽  
pp. 1-10
Author(s):  
Godfather Dickson Kimaro ◽  
Christian Bottomley ◽  
Amos Kahwa ◽  
Lorna Guinness ◽  
Sokoine Kivuyo ◽  
...  
Keyword(s):  
Side Effects ◽  
Low Income ◽  
Home Visits ◽  
Antiretroviral Drugs ◽  
Clinical Staff ◽  
Sub Saharan Africa ◽  
Medical Attention ◽  
People Living With Hiv ◽  
Adherence Support ◽  
Hiv Aids

Introduction: In 2018, there were appropriately 20.6 million [18.2 million–23.2 million] people living with HIV in Eastern and Southern Africa, and an estimated 67% of them were on antiretroviral therapy (ART). A major challenge in the scale-up of ART services in Sub-Saharan Africa is the severe shortage of clinical staff. Methods: We conducted a randomised trial in Tanzania and Zambia to test an innovative intervention that involved the use of lay health workers and screening for cryptococcal meningitis and tuberculosis. Here we describe the model of care with a particular focus on the trained lay worker component. Lay workers carried out home visits to patients in the intervention arm to deliver antiretroviral drugs, provide adherence counselling, and conduct simple monitoring for treatment side effects and other medical conditions. Lay workers were responsible for referring patients with conditions that might require further medical attention as well as discouraging self-referral. A total of 1999 participants were enrolled in the trial. Lay workers were recruited through public advertisements. Results: Six lay workers were recruited in each country and trained for two weeks. Each lay worker was paid a monthly salary of US$ 487.61 in Zambia and US$ 524.61in Tanzania. They were also paid communication and transport expenses for home visits. The median number of visits per patient was 3 for Tanzania and 4 for Zambia. On average a lay worker was responsible for 72.3 patients in Tanzania and 94.5 in Zambia for 1 year. Referrals were made in 9% of the home visits and self-referral was discouraged in 64% of visits. Conclusion: The use of paid lay workers to provide HIV/AIDS services in urban settings where there is a shortage of clinical staff may help to identify ART related side effects/adverse reactions and prevent unnecessary referrals. 

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

PERAN WARGA PEDULI AIDS CAHAYA CARE TUREN DALAM MENINGKATKAN KUALITAS HIDUP ODHA

2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Tri Nurhudi Sasono
Keyword(s):  
Quality Of Life ◽  
Antiretroviral Drugs ◽  
P Value ◽  
People Living With Hiv ◽  
Purposive Sampling ◽  
Significant Difference ◽  
Development Goals ◽  
Living With Hiv ◽  
Hiv Aids

Abstract : Indicator of the health welfare through Sustanable Development Goals (SDGs) is to reduce the incidence of HIV-AIDS, decrease the rate of the epidemic and maintain the quality of life of people living with HIV-AIDS (PLWHA). Trend cases of HIV-AIDS is the most recent spread among people, especially housewives. In Malang until 2015 found 278 Housewife of 409 cases of AIDS. The prevalence of HIV-AIDS in Malang Regency is ranked second after Surabaya city in East Java. For the importance of public participation and citizen care AIDS Cahaya Care Turen take responsibility for the condition. Determination Rule Goverment number 2 2015 year on the Participation of the community response to HIV-AIDS in Malang as a legal rule. Concerned Citizens activities AIDS (WPA). WPA Cahaya Care Turen is increases HIV risk and quality of life PLWHA. The purpose of this study was to determine the role of Citizens AIDS Cahaya Care Quality of Care Turen against people living with HIV in Puskesmas Turen Malang. The study design using a quasi-experimental, with purposive sampling using a sampling technique. Total number of research subjects 23. Based on test results obtained with the Wilcoxon p value <0.005, which means that there is a significant difference before and after PLWHA joining participated in the WPA Cahaya Care Turen. The conclusion of this study is WPA activities involving people living with HIV and at risk groups can optimize compliance with antiretroviral drugs that have an impact on improving the quality of life of PLHIV. Suggestions in this research is done WPA Program activities are structured and ongoing cross-sector in order to improve the quality of life and empower PLWHA.Keywords : WPA Cahaya Care Turen, Quality of life, PLWHA Abstrak : Salah satu indikator kesejahteraan kesehatan melalui Sustanable Development Goals (SDGs) adalah menekan angka kejadian HIV-AIDS, menurunkan laju epidemik dan mempertahankan kualitas hidup Orang dengan HIV-AIDS (ODHA). Trend kasus HIV-AIDS terkini terbanyak adalah menjangkit dikalangan masyarakat khususnya pada ibu rumah tangga. Kabupaten Malang sampai dengan tahun 2015 ditemukan 278 Ibu Rumah Tangga dari 409 kasus AIDS. Prevalensi HIV-AIDS di Kabupaten Malang ini merupakan peringkat kedua di Jawa Timur setelah Kota Surabaya. Untuk itu pentingnya peran serta masyarakat dan warga peduli AIDS Cahaya Care Turen ikut bertanggung jawab terhadap kondisi tersebut. Penetapan Peraturan Bupati Malang no.2 th.2015 tentang Peran serta masyarakat penanggulangan HIV-AIDS di Kabupaten Malang diharapkan dapat mengurangi risiko penularan HIV dan meningkatkan kualitas hidup ODHA. Tujuan dari penelitian ini adalah untuk mengetahui Peran Warga Peduli AIDS Cahaya Care Turen terhadap Kualitas ODHA Di Wilayah Kerja Puskesmas Turen Kabupaten Malang. Desain penelitian menggunakan quasi eksperimen, dengan teknik sampling menggunakan purposive sampling. Jumlah subyek penelitian sejumlah 23. Berdasarkan hasil uji dengan Wilcoxon didapatkan nilai p value < 0.005 yang berarti bahwa terdapat perbedaan bermakna sebelum dan sesudah ODHA bergabung mengikuti kegiatan WPA Cahaya Care Turen. Kesimpulan dalam penelitian ini adalah kegiatan WPA dengan melibatkan ODHA dan kelompok beresiko dapat mengoptimalkan kepatuhan obat ART sehingga berdampak terhadap peningkatan kualitas hidup ODHA. Saran dalam penelitian ini adalah dilakukannya Program kegiatan WPA yang terstruktur dan berkesinambungan lintas sektor guna meningkatkan kualitas hidup dan memberdayakan ODHA.     Kata kunci : WPA Cahaya Care Turen, kualitas hidup, ODHA

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Akhlesh Kumar Jain ◽  
Hitesh Sahu ◽  
Keerti Mishra ◽  
Suresh Thareja
Keyword(s):  
Side Effects ◽  
Liver Cancer ◽  
Entrapment Efficiency ◽  
Xrd Analysis ◽  
In Vitro Cytotoxicity ◽  
Physical Interaction ◽  
Scanning Calorimetry ◽  
Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

Nanoparticles and Its Implications in HIV/AIDS Therapy

2020 ◽  
Vol 17 (4) ◽  
pp. 448-456 ◽  
Author(s):  
Victor B. Oti
Keyword(s):  
Direct Injection ◽  
Oral Intake ◽  
Public Health Problem ◽  
Antiretroviral Drugs ◽  
The Body ◽  
Viral Agent ◽  
Treatment And Prevention ◽  
Prevention And Treatment ◽  
Hiv Aids

The use of Antiretroviral drugs in treating HIV/ AIDS patients has enormously increased their life spans with serious disadvantages. The virus infection still remains a public health problem worldwide with no cure and vaccine for the viral agent until now. The use of nanoparticles (NPs) for the treatment and prevention of HIV/AIDS is an emerging technology of the 21st century. NPs are solid and colloid particles with 10 nm to <1000 nm size range; although, less than 200 nm is the recommended size for nanomedical usage. There are NPs with therapeutic capabilities such as liposomes, micelles, dendrimers and nanocapsules. The particle enters the body mainly via oral intake, direct injection and inhalation. It has been proven to have potentials of advancing the prevention and treatment of the viral agent. Certain NPs have been shown to have selftherapeutic activity for the virus in vitro. Strategies that are novel are emerging which can be used to improve nanotechnology, such as genetic treatment and immunotherapy. In this review, nanoparticles, the types and its characteristics in drug delivery were discussed. The light was furthermore shed on its implications in the prevention and treatment of HIV/AIDS.

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