History and Clinical Development of Nanomedicines, Nanostructure, and Nanoscale Sciences.

Context: Extraordinary advances in the fields of polymer nanoparticle (nano) drug technology, nanomedicines, nanostructures, and nanoscale sciences have played a key role in the healthcare system. New nanodrug complexes have exceptional pharmacological properties with large surface areas that encourage a formulated medication to distribute, absorb, and produce the desired clinical effects. Objective: The current study aimed to review the latest development in the field of nanodrug particles, theranostic, use of noninvasive techniques, and enhancement of retention of nano-theranostic formulations. That helps to develop the innovative pharmaceutical dosage forms. Setting: The latest published data extracted from search engines PubMed, Scopus, Medline, Wolfram Alpha, BASE, Science.gov, Semantic Scholar, Education Resources Information Center, Microsoft Academic, ResearchGate, RefSeek, WorldWideScience, arXiv, Microsoft Academic Search, Google Books, JSTOR, Scirus, Social Science Research Network, Bioline International, SciELO, MetaCrawler, PLOS One, Google Scholar, and Infotopia. Design: The metadata of clinical trials, retrospective, prospective and case control studies collected from the peer review research/ review articles. The aforesaid search engines used to explore the latest information published in ≤200 research studies. the key words Nanomedicines, nanostructure, nanoscale sciences and clinical development run into the system to obtain more specific information. The final data was analyzed, interpreted and narrated for his study. Result: The precisely use of nanodrug for targeted disease produced considerable clinical results. Particularly the designed therapeutic nanoparticle formulations help to reduce the excretion, prolong blood circulation to increase accumulation at a targeted site and increase the therapeutic effects. Conclusions: The nanodrug complexes are successfully translated into several modern medications. The new and innovative nanodrug can potentially be used precisely and correctly to diagnose and treat the terminally ill patients. However, the developed nanodrug complexes, whether they are carriers or therapeutic agents, need thorough physiochemical, pharmacological, and immunological characterization before actual use in clinical practice in different human population of the world.

The Role of Pro-Inflammatory Mediator Interleukin-32 in Osteoclast Differentiation.

The recently explained cytokine, which is produced after the stimulation of interferon (IFN)-c, interleukin (IL)-2, and IL-18 is IL-32, has pro-inflammatory IFN-c, IL-2 and IL-18 are IL-32 mediator's properties that are generally entailed in many diseases, including infections, cancer, and chronic inflammation. After the initial statement in 2005, it promoted the osteoclast precursor's differentiation into TRAcP plus VNR plus multinucleated cells that express explicit osteoclast indicators. Furthermore, the loss of bone resorption might be accredited because of the collapse of the multinucleated cells, which are produced of the reaction to IL-32 to direct factoring that is ultimately essential for attaching the cells for bone resorption. Thus, in conclusion, IL-32, the pro-inflammatory mediator, has an important and indirect role in regulating osteoclast differentiation. In bone disorder's pathophysiology, critical role of IL-32 needs more scientific evidence to develop a rational treatment protocol. IL-32 can become a potent mediator of active osteoclast generation in the presence of receptor activator of NF-κB ligand (RANKL). This novel cytokine can introduce more favorable conditions for osteoclastogenesis in the rheumatic arthritis by increasing the RANKL and osteoprotegerin ratio in fibroblast-like synoviocytes.

Medicinal Plants and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Treatment of Arthritis: A Literature Review.

Context: Arthritis is an inflammatory disease of diarthrodial joints and is associated with swollen inflamed joints, disruption of joints, and loss of integrity of articular cartilage and synovial joints. Objective: The current review intended to examine the data on the epidemiology, causes, clinical diagnosis, and prevention and control of different types of arthritis and on the use of medicinal plants in gouty arthritis. Design: The research team performed a literature review, searching relevant literature databases, including bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, and PubMed. The search terms were arthritis, diarthodial joints, use of medicinal plants in gouty arthritis, and synovial joints. Setting: The study took place in the main library of the University of Sargodha in Sargodha, Pakistan. Results: The research team identified 135 studies, and eventually 92 unique academic publications were included in the analysis. Arthritis can develop and progress in any musculoskeletal joint, and most commonly occurs in knees, hips, shoulders, and hands. Major risk factors for arthritis include age, obesity, trauma, other diseases, and smoking. Arthritis is classified into various types, including rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis, septic arthritis, and psoriatic arthritis (PsA). RA and OA are the most common types worldwide. RA is an autoimmune disease in which the body's immune cells attack the joints. OA develops due to damage of cartilage, tissues, and joints due to age, obesity, or stress on joints. Gouty arthritis develops due to hyperuricemia; deposits of monosodium urate crystals can lead to gouty arthritis. Septic arthritis occurs due to a microbial infection in synovial joints because in synovial joints the basement membrane is absent. PsA develops due to the psoriasis-skin disease. Conclusions: The current review showed that different types of arthritis has different causes and pathogeneses. Pain in joints is a major and common symptom in all types of arthritis. Arthritis is managed pharmacologically and nonpharmacologically. Treatment is different for each class of arthritis according to its cause and symptoms.

The Potentially Recommended Pharmacotherapy for COVID-19.

CONTEXT: A completely unique coronavirus (2019-nCoV), formally referred to as severe acute respiratory syndrome (SARS-CoV-2), appeared in China. SARS-CoV-2 is an etiological mediator of coronavirus 2 (COVID-19), characterized by pneumonic contagion in human beings. In spite of forceful suppression, this virus has spread worldwide. No specific drugs have been approved by the FDA for treating COVID-19 patients. OBJECTIVE: The study intended to examine the data from studies on clinical management of COVID-19. DESIGN: The research team performed a literature review, searching relevant literature databases. The sources of data included bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, WanFang Data, and PubMed. The search terms were treatment of the novel coronavirus, management of nCoV-19, chloroquine, and hydroxychloroquine. SETTING: The study took place in the main library of the University of Sargodha in Sargodha, Pakistan. RESULTS: The study identified 42 unique studies that had reported and confirmed over 1500 cases of nCoV-19 by April 21, 2020. The studies found that clinical management, for patients who presented with symptoms, included supportive care and control measures that comprised mechanical ventilator support and supplementary oxygen. CONCLUSIONS: There have been intensive attempts to explore drug therapy for the prophylaxis and treatment of SARS-CoV-2 infection during this COVID-19 pandemic. Several drugs have been identified which including remdesivir, two antimalarials (chloroquine and hydroxychloroquine) and immunosuppressive agents. The effects of most drug interventions are currently highly uncertain and several drugs and vaccines are under trail for the effective treatment of COVID-19 virus, until an effective treatment will discover social distancing and physical hygiene should be practiced strictly.

Biochemical Dynamics and Clinical Features of Novel Corona Virus (2019-nCoV).

CONTEXT: The novel Corona Virus (nCoV-19) was initially reported in Wuhan, China during December 2019, and later people with nCoV-19 were identified in different parts of the world. Infected people had shown symptoms resembling pneumonia, but about 50% of patients were asymptomatic. OBJECTIVE: The study intended to examine the data from studies on nCoV-19. DESIGN: The research team performed a literature review, searching relevant literature databases. The sources of data included bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, WanFang Data and PubMed. The search terms were novel Corona Virus, and nCoV-19 structure. SETTING: The study took place in the main library of the University of Sargodha, Sargodha, Pakistan. RESULTS: The study identified 22 studies that had reported and confirmed over 2000 cases of nCoV-19 by January 26, 2020. The studies found that the virus was transmitted through respiratory droplets. The virus has two serotypes, OC43 and 229E. CONCLUSIONS: No specific curative therapy is available for CoVid-19. However, certain precautionary measures may potentially reduce the transmission, including washing hands, using sanitizers frequently, avoiding public gatherings, and quarantining or isolating patients. This virus has spread globally and immunocompromised individuals, and especially older individuals, are at significant risk. Community and healthcare professionals have a positive role to play in controlling the spread of the disease.

Formulation, evaluation and in vitro characterization of gastroretentive floating tablet of diclofenac sodium.

Currently a variety of tools and techniques are used to deliver complex medicines. Whereas, certain advanced methods assure the safety and usefulness by regulating the pharmacokinetic and pharmacodynamic. Thus, we aimed this study to develop a novel gastro retentive floating tablets. The formulation was designed to provide the desired controlled and complete release of drug for prolonged period of time. The formulations were evaluated for physical characterization. The obtained results of hardness (4.6-5.1), friability (0.20-0.43%), weight variation (350 ±2 - 350±5) and in vitro buoyancy were found within official limits of United Stated Pharmacopoeia (USP). Whereas, the F-7 showed most optimized intra gastric floating characteristics and exhibited 93.87% release of diclofenac sodium in 9 hours. The Floating Lag Time of 8 minutes and Total Floating Time >12 hours were recorded. In-vitro drug release kinetics evaluated using the linear regression method was found to follow the Zero Order and Peppas model for the release of both the drugs. DSC thermograph and FTIR spectra depicted that there was no chemical incompatibility between drugs and polymers. In conclusion the desgined tablet can be use in clinical practice as model drug. Because, the pre-compression and post-compression parameters were satisfactory and within desired limits.

Monocytopenia; Induction by Vinorelbine, Cisplatin and Doxorubicin in Breast, Non-Small Cell Lung and Cervix Cancer Patients.

BACKGROUND: The neoplasm is still a potential threat for breast, Non-Small Cell Lung (NSCL) and cervix cancer patients. Those gradually invade into other body organs, inducing complex pathological complications. Whereas, the anticancer drugs suppress the bone marrow, resulting serious hematological toxicities. Thus, the monocytic toxicity may the chance of infections, particularly in AID's patients. OBJECTIVE: We aimed this retrospective study to investigate the monocytopenia induced by vinorelbine following chemotherapy in cancer patients. PATIENTS AND METHOD: A total 60 adult cancer patients were divided into two groups; Group-1 patients received the treatment of Vinorelbine alone while group 2 patients received Vinorelbine based combination chemotherapy. RESULT: The overall comparison of mean monocyte count (×103 per µl) with time showed a significant statistical difference (p value <0.001) for G-I and no significant difference for G-II (p value <0.08). The independent comparison of mean values for two groups at every week confirms the non-significant statistical difference during all of the five weeks (p values 0.551, 0.112, 0.559, 0.372, 0.468 respectively). In addition of that, the comparison of mean values observed before therapy with that of week 4 (after therapy) showed significant difference in G-I (p value <0.001) and non-significant in G-II (p value 0.053). CONCLUSION: Monocytopenia is induced in both of the chemotherapy protocols allows the clinical oncologists and consultant physicians to select either of the chemotherapy protocol. The therapeutic efficacy should constitute the intervening consideration to treat the breast, cervix and NSCL (Non-Small Cell Lung's) cancers.

Lymphocytopenia; induced by vinorelbine, doxorubicin and cisplatin in human cancer patients.

Cancer chemotherapy exerts deleterious effects in patients, causing structural and physiological changes to their vital organs. These drugs are capable of destroying bone marrow cells and may reduce lymphocyte count. This study was aimed to investigate the frequency of lymphocytopenia in cancer patients taking vinorelbine and its combination as part of cancer chemotherapy. A total 60 adult cancer patients were selected and divided into two groups; Group-1 patients were either on Vinorelbine alone treatment protocol, while group 2 patients were on either Vinorelbine/Cisplatin or Vinorelbine/Doxorubicin treatment protocol. The mean ± SEM lymphocyte counts (× 10^{3}) per uL, pre and post chemotherapy were noted. The outcomes demonstrated no statistically important difference in the patients who were either on vinorelbine alone, vinorelbine plus cisplatin or vinorelbine plus doxorubicin combinations. On comparison of the lymphocytopenia over time for Group-I & II (P-values 0.064, 0.23), and at every week (P-value -0.063, 0.427), we observed the non significant statistical differences. However, comparison of mean values before with that of at week-1,2 and 3 showed significant (P-value^{3} 0.003, 0.003 and 0.055), and at week-4 no significant difference (P-value^{3} 0.727). Thus, the overall lymphocytopenic syndrome in both of the chemotherapy protocols allows the clinical oncologists and consultant physicians to select either of the chemotherapy protocol. Vinorelbine may be a choice of cancer chemotherapy, as they do not compromise immunity in cancer patients. Hence; therapeutic efficacy should constitute the intervening consideration in treating a particular neoplasm.

Emergence of potential superbug mycobacterium tuberculosis, lessons from new delhi mutant-1 bacterial strains.

Recent reports have shown that certain bacterial strains attain the New Delhi Metallo-beta-lactamase-1 (NDM-1) enzyme and become resistant to a broad range of antibiotics. Similarly, more dangerous "superbugs" of multi-drug resistant (MDR) and extensive drug resistant (XDR) Mycobacterium tuberculosis strains are gradually emerging through rapid genetic mutation caused by prescription non-compliance or unsupervised indiscriminate use of anti-tubercular drugs or other antibiotics. Mycobacterium tuberculosis cases have been reported in highly susceptible population groups including the aboriginal communities of US and Canada. In Canada alone, the total number of reported tuberculosis cases has decreased over the past decade. However, there is a steady increase in HIV cases in certain communities including the aboriginal communities. Reintroduction of MDR/XDR strains of tuberculosis is possible in these susceptible communities, which in turn may pose serious public health situation. MDR/XDR strains of tuberculosis are virtually untreatable using current anti-tubercular medication protocols. Thus, MDR/XDR tuberculosis presents a grave global public health threat. The unpredictable genetic mechanism involved in generating MDR/XDR resistant strains of Mycobacterium tuberculosis may pose greater challenges in developing appropriate treatment strategies. In this article, we briefly review potential genetic mechanism of emerging NDM-1 bacterial strains and draw a rationale parallel to the underlying genetic mechanism of MDR/XDR Mycobacterium tuberculosis strain development.

Ethambutol resistance of indigenous Mycobacterium tuberculosis isolated from human patients

The present study was conducted to find out the ethambutol resistance pattern of indigenous isolates of Mycobacterium tuberculosis from Tuberculosis diagnosed human patients. A total of 172 specimens were collected from six different sources and comprised of 84.9 percent sputum, 10.5 percent pus and 4.7 percent bronchial washings. There were 70.9 percent males and 29.1 percent females with 84.30 percent pulmonary and 15.69 percent extra-pulmonary tuberculosis. The Mycobacterium tuberculosis isolates collected from primary culture were further studied to determine their pattern and level of resistance. The inoculums were prepared using 0.5 Mac Farland turbidity standards. Five different concentration of ethambutol were used in Lowenstein Jensen (LJ) medium i.e. 2μg/ml, 4μg/ml, 6μg/ml, 8μg/ml and 10μg/ml for sensitivity testing. Data showed 10 (5.8 percent) resistant and 162 (94.2 percent) sensitive Mycobacterium tuberculosis out of total 172 clinical isolates. The growth was not inhibited at 1st (2μg/ml) and 2nd (4μg/ml) drug levels, while growth of 50 percent isolates inhibited at 3rd level (6μg/ml), 30 percent inhibited at 4th level (8μg/ml) and 20 percent at 5th level (10μg/ml). The last three levels are above the therapeutic index and not recommended in actual clinical practice. It is thus conceivable to explore some other more effective chemotherapeutic agents, modify combinations or find more effective procedures to stop morbidity and mortality due to ethambutol resistant Mycobacterium tuberculosis.

Ethambutol resistance of indigenous Mycobacterium tuberculosis isolated from human patients.

The present study was conducted to find out the ethambutol resistance pattern of indigenous isolates of Mycobacterium tuberculosis from Tuberculosis diagnosed human patients. A total of 172 specimens were collected from six different sources and comprised of 84.9% sputum, 10.5% pus and 4.7% bronchial washings. There were 70.9% males and 29.1% females with 84.30% pulmonary and 15.69% extra-pulmonary tuberculosis. The Mycobacterium tuberculosis isolates collected from primary culture were further studied to determine their pattern and level of resistance. The inoculums were prepared using 0.5 Mac Farland turbidity standards. Five different concentration of ethambutol were used in Lowenstein Jensen (LJ) medium i.e. 2µg/ml, 4µg/ml, 6µg/ml, 8µg/ml and 10µg/ml for sensitivity testing. Data showed 10 (5.8%) resistant and 162 (94.2%) sensitive Mycobacterium tuberculosis out of total 172 clinical isolates. The growth was not inhibited at 1(st) (2µg/ml) and 2(nd) (4µg/ml) drug levels, while growth of 50% isolates inhibited at 3(rd) level (6µg/ml), 30% inhibited at 4(th) level (8µg/ml) and 20% at 5(th) level (10µg/ml). The last three levels are above the therapeutic index and not recommended in actual clinical practice. It is thus conceivable to explore some other more effective chemotherapeutic agents, modify combinations or find more effective procedures to stop morbidity and mortality due to ethambutol resistant Mycobacterium tuberculosis.