Bedaquiline: An Insight Into its Clinical Use in Multidrug-Resistant Pulmonary Tuberculosis.

Every year, the World Health Organization reports 500,000 new cases of drug-resistant tuberculosis (TB), which poses a serious global danger. The increased number of XDR-TB and MDR-TB cases reported worldwide necessitates the use of new therapeutic approaches. The main issues with the antitubercular medications now in use for the treatment of multidrug-resistant tuberculosis are their poor side effect profile, reduced efficacy, and antimicrobial resistance. One possible remedy for these problems is bedaquiline. The need for better treatment strategies is highlighted by the strong minimum inhibitory concentrations that bedaquiline (BDQ), a novel anti-TB medicine, exhibits against both drug-resistant and drug-susceptible TB. Bedaquiline may be able to help with these problems. Bedaquiline is a medication that is first in its class and has a distinct and particular mode of action. Bedaquiline is an ATP synthase inhibitor that is specifically directed against Mycobacterium tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4. Bedaquiline preclinical investigations revealed intralesional drug biodistribution. The precise intralesional and multi-compartment pharmacokinetics of bedaquiline were obtained using PET bioimaging and high-resolution autoradiography investigations. Reduced CFU counts were observed in another investigation after a 12-week course of therapy. Meta-analyses and systematic reviews of phase II trials on bedaquiline's efficacy in treating drug-resistant tuberculosis in patients reported higher rates of cure, better culture conversion, and lower death rates when taken in conjunction with a background regimen. Here is a thorough medication profile for bedaquiline to aid medical professionals in treating individuals with tuberculosis.

Preclinical Safety Assessment of Lepidium sativum L. Seed Extract and its Nanoparticles via Acute and Subacute Oral Administration.

BACKGROUND: Lepidium sativum (LS) seed extract has various pharmacological properties, such as antioxidant, hepatoprotective, and anticancer activities. However, the translation of L. sativum seed extract to the clinical phase is still tedious due to its bioavailability and stability issues. This problem can be solved by encapsulating it in a nanodelivery system to improve its therapeutic potency. METHODS: In this study, we have determined and compared the in vivo toxicity of ethanolic extracts of L. sativum seeds (EELS) and solid lipid nanoparticles (SLNs). To conduct toxicity (acute and subacute toxicity) assessments, EELS and SLNs were orally administered to Swiss albino mice. Animal survival, body weight, the weight of vital organs in relation to body weight, haematological profile, biochemistry profile, and histopathological alterations were examined. RESULTS: Animals administered with 2000 mg/kg and 5000 mg/kg in an acute toxicity study exhibited no toxicological symptoms regarding behaviour, gross pathology, and body weight. As per a study on acute toxicity, the LD50 (lethal dose) for SLNs and EELS was over 400 mg/kg and over 5000 mg/kg, respectively. When animals were given SLNs (50 and 100 mg/kg, orally) and EELS (250, 500, and 1000 mg/kg, orally) for 28 days, subacute toxicity study did not exhibit any clinical changes. There were no differences in weight gain, haematological parameters, or biochemical parameters compared to the control groups (p > 0.05). The organs of the treated animals showed no abnormalities in the histological analysis (liver, heart, kidney, and spleen). CONCLUSION: The result confirms ethanolic extracts of L. sativum seeds and their SLNs to not have harmful effects following acute and subacute administration to mice. For further studies, patents available on Lepidium may be referred for its preclinical and clinical applications.

Curcumin Nanogel Preparations: A Promising Alternative for Psoriasis Treatment.

Curcumin is a naturally occurring polyphenolic compound extracted from the rhizomes of Curcuma longa, commonly known as turmeric. It has been used for centuries in traditional medicine and is gaining increasing attention in modern medicine owing to its potential therapeutic benefits. Psoriasis is a chronic inflammatory disease characterized by red scaly patches on the skin. Curcumin has been found to be effective in treating psoriasis by inhibiting the activity of various enzymes and proteins involved in the inflammation and proliferation of psoriatic skin cells. Nanogel preparation of curcumin has been found to be a promising approach for the delivery of compounds to treat psoriasis. Nanogels are composed of biocompatible and biodegradable crosslinked hydrogels. The nanogel formulation of curcumin increases its solubility, stability, and bioavailability, indicating that a lower dose is needed to achieve the same therapeutic effect. This review article suggests that the nanogel preparation of curcumin can be a better alternative for psoriasis treatment as it increases the bioavailability and stability of curcumin and also reduces the required dosage. This study suggests that curcumin nanogel preparations are promising alternatives to traditional psoriasis treatments and could potentially be used as a more effective and safe treatment option. This article highlights the need for further research to fully understand the potential of curcumin nanogel preparations for psoriasis treatment in humans.

Factors influencing the intention to purchase health insurance: a study of Indian tobacco and alcohol consumers.

Introduction: This study empirically investigates the attitude of tobacco and alcohol consumers towards health insurance purchase in India. The study aims to determine the factors which plays a significant role in determining the purchase intention of health insurance among tobacco and alcohol consumers. Methods: We propose an extended theory of planned behavior (TPB) model comprising factors like attitude, subjective norms, perceived behavior control, perceived usefulness, perceived product risk, and intention to purchase. We collected responses from 420 tobacco and alcohol consumers through a Google Form link shared via different social media platforms. SPSS has been used to perform exploratory factor analysis, whereas AMOS has been used to validate the constructs, confirm the relationships among the variables, and analyze the data. Results: The analysis outcomes demonstrate that subjective norms, perceived product risk, and perceived behavioral control are the factors that have a positive and significant effect on health insurance purchase intention among consumers. Discussion: This research offers valuable insights to the insurance sector, government officials, policymakers, and academicians. Insurance companies may consider the criteria analysed when creating policies to promote the expansion of the health insurance sector.

Diabetic Neuropathy: An Overview of Molecular Pathways and Protective Mechanisms of Phytobioactives.

Diabetic neuropathy (DN) is a common and debilitating complication of diabetes mellitus that affects the peripheral nerves and causes pain, numbness, and impaired function. The pathogenesis of DN involves multiple molecular mechanisms, such as oxidative stress, inflammation, and pathways of advanced glycation end products, polyol, hexosamine, and protein kinase C. Phytochemicals are natural compounds derived from plants that have various biological activities and therapeutic potential. Flavonoids, terpenes, alkaloids, stilbenes, and tannins are some of the phytochemicals that have been identified as having protective potential for diabetic neuropathy. These compounds can modulate various cellular pathways involved in the development and progression of neuropathy, including reducing oxidative stress and inflammation and promoting nerve growth and repair. In this review, the current evidence on the effects of phytochemicals on DN by focusing on five major classes, flavonoids, terpenes, alkaloids, stilbenes, and tannins, are summarized. This compilation also discusses the possible molecular targets of numerous pathways of DN that these phytochemicals modulate. These phytochemicals may offer a promising alternative or complementary approach to conventional drugs for DN management by modulating multiple pathological pathways and restoring nerve function.

Why do academicians share knowledge? A study of higher education institutions in India.

Purpose: Indian higher education institutions are diverse in nature; there are institutions with good infrastructure and resources as well as institutes that have little in terms of resources and infrastructure. Keeping in mind the relevance of knowledge sharing in academic institutions, the researchers in the present study have tried to find factors determining the knowledge sharing behavior of the academicians of different institutes in India. Design: The researchers in the present work have expanded on extant research by demarcating factors that affect the knowledge sharing behavior of academicians. A structured questionnaire was shared through e-mail and social media groups, and a snowball approach was used to reach out to the maximum number of respondents. Findings: The present study offers an integrated and extended theory of planned behavior (TPB) theoretical model, augmenting it with constructs such as motivation and the opportunity to share knowledge adapted from related studies. The findings of this research provide theoretical as well as practical suggestions in determining and explaining the knowledge sharing behavior of academicians. Originality: The researchers in the present study have tried to present a shorter and more reliable scale that can be used to assess the behavioral intentions of academicians to share knowledge.

Consequence of Dementia and Cognitive Impairment by Primary Nucleation Pathway.

An acquired loss of cognition in several cognitive domains that is severe enough to interfere with social or professional functioning is called dementia. As well as a moderately in-depth mental status examination by a clinician to identify impairments in memory, language, attention, visuospatial cognition, such as spatial orientation, executive function, and mood, the diagnosis of dementia requires a history evaluating for cognitive decline and impairment in daily activities, with confirmation from a close friend or family member. The start and organization of the cognitive assessment can be helped by short screening tests for cognitive impairment. Clinical presentations show that neurodegenerative diseases are often incurable because patients permanently lose some types of neurons. It has been determined through an assessment that, at best, our understanding of the underlying processes is still rudimentary, which presents exciting new targets for further study as well as the development of diagnostics and drugs. A growing body of research suggests that they also advance our knowledge of the processes that are probably crucial for maintaining the health and functionality of the brain. We concentrate on a number of the animal models of memory problems that have been mentioned in this review article because dementia has numerous etiologies. Serious neurological impairment and neuronal death are the main features of neurodegenerative illnesses, which are also extremely crippling ailments. The most prevalent neurodegenerative disorders are followed by those primary nucleation pathways responsible for cognitive impairment and dementia.

Sustainable Behavior with Respect to Managing E-Wastes: Factors Influencing E-Waste Management among Young Consumers.

With the proliferation of technological tools and the advancement in electronic devices and accessories, consumers across the world are changing and upgrading their electronic devices at an alarming rate. However, these developments have raised concerns related to electronic waste (E-waste). E-wastes contain toxic substances which may have a negative impact on both humans and the environment. This issue needs to be addressed by the research community, i.e., what would be the best way to get rid of existing devices? It is clear that countries need to work towards a more sustainable consumption pattern and consumers need to change their behaviour. The present study focuses on sustainable behaviour of consumers in terms of e-waste management. In this context, the study attempts to explore the factors influencing e-waste management among young consumers. In the present study, the Theory of Planned Behavior is extended by including the additional factors Government Policy, Environmental Concern, Financial Benefits and Awareness. A researcher-controlled sampling was employed to collect data from 524 respondents. Partial least square structural equation modelling (PLS-SEM) was used to validate the questionnaire constructs and confirm the relationships among the variables. The findings of the study suggest a significant role for government policy, financial benefits, environmental concerns, attitude, subjective norms, and perceived behavioural control in determining young consumers' behavioural intentions toward the management of e-waste. The study findings have implications for both researchers and marketing practitioners.

OdorTAM: Technology Acceptance Model for Biometric Authentication System Using Human Body Odor.

Body odor is a biometric feature unique to each individual, and it can be used for authentication. However, decision makers must learn about the users' level of acceptance of this technology, as well as their thoughts on the system's features and procedures. In this study, a technology acceptance model (TAM) for body-odor-based biometric techniques named OdorTAM was proposed and validated. An English language questionnaire was developed in a web-based, easy-to-read format on Google Forms. The survey consisted of 19 questions, and 150 responses were received. Statistical analysis of the responses was carried out, and it was found that all the hypotheses were supported. Therefore, the OdorTAM model appears to be satisfactory. To this end, we posit that a body-odor-based biometric technique can be one of the alternatives for authentication, and it can also be used along with some other techniques for improved security. The study contributes to the literature on consumers' understanding of biometric technologies, in particular odor detection, which has received relatively less attention in extant research.

Solid Lipid Nanoparticles of Lepidium Sativum L Seed Extract: Formulation, Optimization and In vitro Cytotoxicity Studies.

The current study focused on important bioactive compounds in plants that make them pharmacologically valuable. Therefore, this study was aimed to develop Lepidium sativum (L. sativum) seed extract loaded solid lipid nanoparticles and explore its cytotoxic effect on human liver cancer cells (HepG2 cells). The ethanolic extract of L. sativam used to develop L. sativum seed extract loaded solid lipid nanoparticles (SLNs) was analyzed by gas chromatography-mass spectrometry, thin-layer chromatography (TLC) and high-performance thin-layer chromatography (HPTLC) for phytochemical profiling. The L. sativum seed extract loaded SLNs were efficaciously prepared by the nanoprecipitation method and screened on the basis of physicochemical properties. The L. sativum seed extract loaded SLN-2 was characterized using various parameters like particle size (237.1±0.104), % entrapment efficiency (80±1.15), zeta potential (42.1±0.102) and % drug release (45% at the end 8 hours and release the entire amount in 12 h). The SLN-2 formulation was optimized based on the recipient factor, and SLN-2 was used to further evaluate the in vitro cytotoxicity of HepG2 cells in a dose-dependent manner by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. The IC50 value of SLN2 was 52.37 ug/ml and sub IC50 26.1 ug/ml at 24 h and 48 h, respectively. Thus, we concluded that L. sativum extract loaded SLN-2 could act as an alternative therapy, possibly controlling therapeutic action by making a substantial reduction in side effects.

Frequency of CD34 and CD10 Expression in Adolescent and Young Adult Patients Having Precursor B-cell Acute Lymphoblastic Leukemia and Its Correlation With Clinical Outcomes: A Single-Center Study.

BACKGROUND: The clinical outcomes of CD34 and CD10 antigens expression in adolescent and young adult (AYA) precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) is not still well established. In the present study, we analyzed the laboratory characteristics and clinical outcomes of 123 AYA pre-B-ALL patients in order to evaluate the possible clinical significance of these markers. MATERIALS AND METHODS: In the current study clinical data of 123 consecutive AYA pre-B-ALL patients aged 18-39 years old, enrolled in adult hematology-oncology unit from December 2014 to April 2019 was analyzed. Patient clinical outcome was calculated as overall survival and disease-free survival. RESULTS: Overall, 76.4% of patients showed CD34 expression and CD10 expression was found in 90.2%. CD34 and CD10 expression was associated with higher total leucocyte count, increased peripheral blood blast percentage, and decreased platelet count. Overall survival and disease-free survival were both significantly better in CD34 negative and CD10 negative patients compared to their CD34 positive and CD10 positive counterparts. INTERPRETATION AND CONCLUSION: Expressions of CD34 and CD10 are adverse prognostic factors in AYA pre-B-ALL patients and the presence of these antigens influences the clinical outcome of these patients.

Body Mass Index and Other Risk Factors Effects on Colon Cancer Prognosis in Pakistan.

Introduction: Asian developing countries share the burden of colorectal cancer (CRC) with rising mortality rates. This prospective study aims to apprehend the clinical relevance of age, gender, lifestyle choices (dietary habits and addiction) and body mass index (BMI) to the occurrence and progression of colon cancer (CC). Methods: A cohort of non-cancer (NC) and CC patients of South-Central Asian origin registered for screening colonoscopy or surgery at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC), Lahore, Pakistan, from 2015 to 2020 was identified. BMI (Kg/m2) was classified according to the World Health Organization criteria as underweight (<18.5 Kg/m2), normal weight (18.5-24.9 Kg/m2) and overweight (≥25 Kg/m2). Results: Among 236 participants, 99 (41.9%) belonged to the NC group, and 137 (58.1 %) participants had CC Overall, participants included 74 women and 162 men aged 20-85 years (mean ± SD; 49.9 ± 14.9). Notably, 46.0% of cancer patients had a family history of cancer. There was a direct relationship between CC with abnormal BMI (underweight and overweight), positive smoking history and positive family history of cancer. Conclusion: Being underweight or overweight is a potential risk factor for CC patients. The overall survival in patients with CC is clinically associated with lifestyle choices before CC diagnosis. A balanced diet, walking and other forms of exercise should be strongly recommended to the community and those undergoing screening colonoscopy.

Hematological Parameters and Demographic Distribution of Hemoglobinopathies and Various Hemoglobin Variants.

Background The study was conducted to find the prevalence of hemoglobinopathies along with their geographical/ethnic distribution to highlight the region of high prevalence that can be used to guide screening. Method Results of blood samples received for hemoglobin variants determination by high-performance liquid chromatography (HPLC) were retrospectively analyzed at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore. Blood samples were assayed for CBC (complete blood count), red blood cell morphology, and hemoglobin analysis by HPLC. CBC was performed on Sysmex XN 9000 analyzer (Sysmex, Kobe Japan), peripheral smears to review RBC morphology were stained with Wright-Giemsa stain, and HPLC was performed on BIO-RAD variant II (Bio-Rad Laboratories, Hercules, USA). Results Hemoglobinopathies were identified in 9.7% (n=997) out of 10,297 samples. Beta thalassemia trait was the most common hemoglobinopathy recognized with a prevalence of 5% (n=516), with the maximum number of cases in the Lahore district of Punjab province. The next most common hemoglobinopathy identified was sickle cell disease with a frequency of 1.43% (n=148) and the maximum cases from the Dera Ismail Khan district of the Khyber Pakhtunkhwa province. The additional important hemoglobinopathies found were sickle cell trait, hemoglobin-D Punjab trait, and compound heterozygote for sickle and beta thalassemia. Conclusion Hemoglobinopathies are the most common inherited disorders in Pakistan and worldwide. Screening for hemoglobinopathies is recommended in high-prevalence districts of Pakistan. Sickle cell screening is also recommended in newborns in the high prevalence area of Pakistan, such as the northwest regions.

A Panoramic Review on Lepidium sativum L. Bioactives as Prospective Therapeutics.

BACKGROUND: Lepidium sativum (L. sativum), an annual herb belonging to family Brassicaceae is commonly known as Garden cress of Egyptian origin but now a day's cultivated worldwide. The plant material and its constituents are used in various traditional and folk medicines for the treatment of various liver diseases and other ailments. OBJECTIVE: This review aims to gather comprehensive information on L. sativum's bioactive constituents, and it's antioxidant, hepato-protective and anticancer activity. METHOD: Systematic exploration for research evidences were carried out using well-structured and focused review question and presented data in the tabular form for readers' convenience. RESULTS: The comprehensive literature survey was conducted, and we found that specific studies on L. Sativum and its bioactive compounds had been carried out to date. We explored the unique and selective effect of L. Sativum and its bioactive constituents to combat oxidative stress and hepatic carcinoma. CONCLUSION: The present article appraised that L. sativum extract has a potential therapeutic effect against liver toxicity and hepato-carcinoma. Graphical Abstract.

Antimicrobial susceptibility patterns among community and health care acquired carbapenem resistant Enterobacteriaceae, in a tertiary care hospital of Lahore.

OBJECTIVE: To compare the disk susceptibility pattern of healthcare acquired carbapenem-resistant enterobacteraceae with that of community-acquired isolates and their associated clinical presentations. METHODS: The cross-sectional study was conducted at the Department of Microbiology, Combined Military Hospital, and the Institute of Dentistry, Lahore, Pakistan, from November 2017 to July 2018. Patients with positive carbapenem-resistant enterobacteraceae cultures from clinical specimens were included. All the isolates were identified through conventional methods and standard biochemical tests. Antibiotic susceptibility testing was performed by Kirby Bauer Disk Diffusion method on Muller Hinton Agar plates. Data was analysed using SPSS 23. RESULTS: Of the 123 isolates identified, 97(79%) were healthcare acquired and 26(21%) were community-acquired. Statistically significant susceptibility patterns (p<0.001) of community acquired isolates were observed against cefoperazone-sulbactum and amikacin, while a low significance was observed with gentamycin (p<0.05). Significant results were obtained in case of colistin against both the groups (p<0.001). CONCLUSIONS: There was low antimicrobial resistance in community acquired carbapenem-resistant enterobacteraceae isolates.

Proteomics analysis of colon cancer progression.

BACKGROUND: The aim of this pilot study was to identify proteins associated with advancement of colon cancer (CC). METHODS: A quantitative proteomics approach was used to determine the global changes in the proteome of primary colon cancer from patients with non-cancer normal colon (NC), non-adenomatous colon polyp (NAP), non-metastatic tumor (CC NM) and metastatic tumor (CC M) tissues, to identify up- and down-regulated proteins. Total protein was extracted from each biopsy, trypsin-digested, iTRAQ-labeled and the resulting peptides separated using strong cation exchange (SCX) and reverse-phase (RP) chromatography on-line to electrospray ionization mass spectrometry (ESI-MS). RESULTS: Database searching of the MS/MS data resulted in the identification of 2777 proteins which were clustered into groups associated with disease progression. Proteins which were changed in all disease stages including benign, and hence indicative of the earliest molecular perturbations, were strongly associated with spliceosomal activity, cell cycle division, and stromal and cytoskeleton disruption reflecting increased proliferation and expansion into the surrounding healthy tissue. Those proteins changed in cancer stages but not in benign, were linked to inflammation/immune response, loss of cell adhesion, mitochondrial function and autophagy, demonstrating early evidence of cells within the nutrient-poor solid mass either undergoing cell death or adjusting for survival. Caveolin-1, which decreased and Matrix metalloproteinase-9, which increased through the three disease stages compared to normal tissue, was selected to validate the proteomics results, but significant patient-to-patient variation obfuscated interpretation so corroborated the contradictory observations made by others. CONCLUSION: Nevertheless, the study has provided significant insights into CC stage progression for further investigation.

Granulocyte-colony stimulating factor in neonatal sepsis with leukopenia: A prospective cohort study.

OBJECTIVE: To observe the duration for normalization of the Total Leucocyte Count (TLC) with adjuvant Granulocyte-Colony Stimulating Factor (G-CSF) treatment in leukopenic neonatal sepsis, and to compare the neutrophilic response to G-CSF in neutropenic vs non-neutropenic subgroups. METHODS: This prospective cohort study was carried out at the Neonatal Intensive Care Unit at Military Hospital Rawalpindi (NICU) from 1st August 2015 to 25th January 2017. Fifty one newborns with sepsis and leucopenia were sampled judgmentally from a population of 5666 admitted to NICU during the study period. The sample was then divided into neutropenic (exposed) and non-neutropenic (non-exposed) subgroups on basis of the absolute neutrophil count (ANC). Adjuvant G-CSF was given to all subjects and stopped once TLC normalized. SPSS v22 was used to calculate mean G-CSF treatment duration and rise in ANC. A Pearson correlation coefficient and simple linear regression were computed to assess the relationship between pre-GCSF ANC and the duration of treatment with GCSF. Comparison of subgroups with respect to rise in ANC was done using independent samples T-test. RESULTS: The mean duration of G-CSF treatment was 1.82±0.81 days (1.0 - 4.0). Neutropenic neonates constituted 49% (n=25). The Pearson correlation coefficient showed a positive but negligible and non-significant correlation between the two variables, r = 0.070, n = 51, p = 0.625. A non-significant regression equation was found (F(1,49) = 0.242,p=0.625) with an R2 of 0.005. There was a 7.06±4.5 fold rise in ANC in the neutropenic subgroup compared to the 4.5±3.1 fold rise in the non-neutropenic subgroup (p=0.04). CONCLUSIONS: The mean duration for recovery from leukopenia with G-CSF treatment in neonatal sepsis was less than 2 days and had no significant relationship with pre-GCSF absolute neutrophil count. The neutrophilic response was significantly higher in neutropenic compared to non-neutropenic neonates. As GCSF made no difference to the outcome in terms of mortality, its routine use is not recommended in leukopenic neonatal sepsis. .

Nigella sativa L. and Its Bioactive Constituents as Hepatoprotectant: A Review.

BACKGROUND: The pharmacological properties of Nigella sativa L. are well attributed to the presence of bioactive compounds, mainly, thymoquinone (TQ), thymol (THY) and α hederin and their antioxidant effects. TQ, THY and alpha-hederin (α-hederin) provide protection to liver from injury via different mechanisms including inhibition of iron-dependent lipid peroxidation, elevation in total thiol content and (GSH) level, radical scavenging, increasing the activity of quinone reductase, catalase, superoxide dismutase (SOD) and glutathione transferase (GST), inhibition of NF-κB activity and inhibition of both (COX) and (LOX) protects liver from injuries. Review and Conclusion: The main aim of this literature review is to reflect the relevant role of ROS in inducing hepatic diseases and also the preventive role of N. sativa L. in hepatic diseases. The present article is directed towards highlighting the beneficial contribution of researchers to explore the pharmacological actions with therapeutic potential of this precious natural herb and its bioactive compounds pertaining to the hepatoprotective effects. We systematically searched for research literature through well-framed review question and presented the data in the tabular forms for the convenience of the readers. Two hundred and forty-one papers were embodied in this review, oxidative effect and the reactive oxygen species (ROS) are known to be the major causes of many diseases such as hepatic cancer. Many drugs and chemicals have shown to incite oxidative damage by generation of ROS in the body. Therefore, this review intends to focus the role of ROS in liver diseases and the mechanisms through which N. sativa prevents hepatic diseases. The mechanisms by which N. sativa impede progression in chronic liver diseases should be used as a preventive medicine in patients with hepatic disorders.