New Insights into Disease and Pathogen Research Vol. 2

Extrapulmonary Tuberculosis- A Diagnostic Conundrum!

2021-07-30T03:43:48+00:00

Introduction: Tuberculosis continues to be the ninth leading cause of death worldwide. Pulmonary tuberculosis [PTB] being an infectious form of the disease receives greater attention & significance; while, the silent forms of disease like latent tuberculosis infection [LTBI] or extrapulmonary [EPTB] form of disease remains as the most neglected ones for reasons well known. Exact data on the disease burden from developing countries is missing due to the existing poor reporting system by both the patient and health care services.

Aim: To know the burden of the disease in a tertiary care hospital of India. To study the clinical trends in the disease, and the utility of various diagnostic modalities in diagnosis of the same. To identify the Mycobacterial species and perform drug susceptibility test.

Materials and Methods: A cross sectional study was carried out for a period of two years. A total of 147 samples were received and tested for extrapulmonary tuberculosis using a combination of bacteriological, cytological, histological and biochemical techniques to achieve proper diagnosis of EPTB.

Results: Bacteriologically, 26% of the specimens were positive for EPTB. Mycobacterial culture positivity was noted in 18%. Smear by Ziehl Nielsen stain was positive in 9%. Young adults and females predominated the study group and positive cases. A combination of culture media both solid and liquid maximized the yield of Mycobacteria. Lymph node tuberculosis was found to be the predominant type followed by others. Fifteen percent of the strains were found to be resistant to the first line drugs used in treatment of tuberculosis. Cytology and biochemical findings were found to be less specific in diagnosis of extrapulmonary tuberculosis. Rapid immuno chromatographic test called MPT64 Antigen test was very useful for presumptive identification of M.tb complex with reported sensitivity and specificity of 99% and 100%.

Conclusion: Extra pulmonary tuberculosis is seen in a substantial number of the symptomatic patients. Hence, attention should be paid towards its proper and early diagnosis followed by rational management, as if neglected may lead to associated complications and sequalae. Use of combination of media and methods enhances the diagnostic sensitivity. Further research is needed to evaluate specific reasons for why the disease is more common in young adults and females. It is wiser to read cytology and biochemical findings in light of bacteriological results as alone they are less specific. Resistance is emerging to anti tuberculosis drugs even in extra pulmonary form of disease. Hence the use of anti-tuberculosis drugs has to be justified as per the laboratory results for drug susceptibility test.

Risk Factors for Developmental Dysplasia of The Hip

2021-07-30T03:56:50+00:00

Aims: To identify the association between potential risk factors with developmental dysplasia of the hip in neonates.

Study Design: A cross-sectional study.

Place and Duration of the Study: Laboratory of Lifestyle, Division of Health Sciences and Engineering, Campus Celaya Salvatierra, University of Guanajuato Mexico, between June 2014 and February 2015.

Methodology: We include 100 newborns, 36 male and 64 females with age between 4 and 28 days old. Data on birth weight, family history of hip dysplasia, obstetric presentation, mode of delivery, swaddling was obtained. The diagnosis of hip dysplasia hip ultrasonography with Graf technique was confirmed. For association Chi squared and p value, for the effect was calculated Odds Ratio and confidence intervals at 95%.

Results: It was found that obstetric presentation and swaddling were associated with developmental dysplasia of the hip (p <0.05) with OR of 5.32 and 4.91 respectively, and the association was confounded by area of residence with OR adjusted 2.94.

Conclusion: It was conclude that the most important risk factors for developmental dysplasia of the hip in this population were obstetric presentation and excessive swaddling.

Medication Errors Identification: A Major Source of Evaluating Prescribing Errors in Liver Disease Patients

2021-07-30T04:10:09+00:00

Aim: The aim of this study was to retrospectively review the patient profiles with liver diseases in order to determine the frequency of medication errors among patients with liver diseases.

Study Designed: Retrospective study was performed.

Place and Duration of Study: Abbasi Shaheed Hospital (ASH), Civil Hospital (CIVIL) and Dow University Hospital (DUH) Karachi Pakistan, conducted from April 2014 to June 2014.

Methodology: The retrospective study was conducted by evaluating 61 patient profiles. These patients were admitted in three different hospitals of Karachi city mentioned above. Toxic hepatitis or drug-induced liver injury comprises a spectrum of clinical diseases that initiates with mild biochemical abnormalities and extends to acute liver failure. In this study 61patient’s profiles were collected and evaluated. The patients were aged 25 years and above. A quantitative analysis and investigation of clinically significant drug-drug interactions, drug-disease interactions, inappropriate medication, over dose and sub therapeutic dose has been studied. Moreover these patients were suffering from either hepatitis B, hepatitis C, hepatitis E, ascites, jaundice, liver abscess, hepatoma, chronic liver disease (CLD), cirrhosis, hepatic encephalopathy or acute hepatitis.

Results: A total 257 medication errors were observed, out of which 40% (n=102) were drug-drug interactions, 14.5% (n=37) were drug-disease interactions, 37.7% (n=97) were inappropriate medications, 7.05% (n=18) were related to over-dose and 1.17% (n=3) were identified as sub-therapeutic dose errors. The occurrence of different types of medication errors was significantly different among the named hospitals.

Conclusion: It can be concluded that a large number of medication errors in a minimal patient’s profiles were observed. This shows a high percentage of irrational prescribing practice among liver disease patients. Furthermore, there is a need to revise the proper structure of hospital and clinical pharmacies. Additionally, the proper prescribing patterns should be followed via employing computerized physician order entry system (CPOE). The result of our study shows high number of medication errors. The rate of medication errors can be minimized by inclusion of clinical pharmacists in hospitals because pharmacist can play a vital role in the identification and prevention of medication errors and can educate all health care professionals with up-to-date information related to drugs. Implementation of electronic based system like COPE system can be beneficial to minimize the chances of errors and it is also essential to educate the patients about their medications along with Staff orientation/development in order to reduce the possibility of these errors.

Evaluation of Outcome of a Rare Presentation of Appendicitis

2021-07-30T04:12:28+00:00

Introduction: Acute appendicitis is the inflammation of the vermiform appendix and it is the most common intra-abdominal surgical emergency. Therefore, perforated appendicitis is rarely accompanied by pneumoperitoneum and that apparent rarity of association of pneumoperitoneum and acute appendicitis prompted us to discuss this condition.

Materials and Methods: This retrospective study reviewed all cases of acute abdomen with pneumoperitoneum admitted in King Abdulaziz University Hospital from January 2011 to December 2015. Only cases with acute appendicitis were selected to be in the study, Leucocytic count and C-reactive protein, as well as plain X-ray abdomen in erect position and C.T.scan were reviewed preoperatively.

All demographic data (age, gender), as well as the clinical details which included relevant investigations results, in addition to the perioperative data (the type of the performed operative procedure, operative time and the hospital stay with reference to the postoperative complications for each patient), all were collected and analyzed by IBM-SPSS version 22.

Results: Pneumoperitoneum due to perforated appendix was found in 7 out of 131 cases in this study (5.3%), with male predominance 6/7, with a mean age of 29.7 years. The documented postoperative complications were pulmonary complications; intra-abdominal pus collection (pelvic and subphrenic) as well as wound dehiscence, all were found post conventional exploratory laparotomy cases.

Conclusion: The study documented the rarity of pneumoperitoneum due to perforated appendix. Therefore, it should be considered as a cause of acute abdomen with pneumoperitoneum, imaging studies were very essential to visualize these cases, Laparoscopic approach provided better outcome than the conventional laparotomy approach.

Prevalence of Hypertension Stages and the Main Risk Factors in Khartoum Locality, Sudan, 2014

2021-07-30T04:23:39+00:00

Background Information: Cardiovascular diseases (CVDs) are number one killer in the world among non-communicable diseases (NCDs). The principal underlying risk factor for CVDs is hypertension (HTN).

Objectives: To identify the prevalence of hypertension, the stages of HTN and the related risk factors such as age, sex, smoking and body mass index (BMI) among the population in Khartoum locality, Sudan, 2014

Methods: A community based cross-sectional study was carried out in Khartoum locality during March- April 2014. A total of 948 adult individual were interviewed using structured questionnaire that was filled by medical officers, house officers and semi-final medical students. Blood pressure (BP) was measured twice with 5-6 minutes in-between. Hypertension was considered as ≥ 140 mmHg and ≥ 90 mmHg for systole and diastole BP respectively. The international classification of BMI was used for underweight, normal, overweight and obesity.

Analysis: Prevalence of HTN and the stages was measured by descriptive statistics. Multiple logistic regressions was used to test relationships of age, sex, smoking and BMI with stages of hypertension, pre-HTN, stage one HTN, stage two HTN, isolated systolic hypertension (ISHTN) and isolated diastolic hypertension (IDHTN).

Results: More than half of the population (51.3%) was in the age group 18-36 years. Males and females account to 44.7% and 55.3% respectively. Overweight and obesity was detected in 59.1% of the study population. Most of the study populations were non-smokers (88.8%). Pre-HTN, HTN (stage one and two), ISHTN and IDHTN were 7.7%, 10.7%, 9.4% and 7.9 respectively.

Smoking contributed to occurrence of pre-HTN by 5.7%. It has no contribution to other stages of HTN. Male sex is the contributing factor for occurrence of pre-HTN, stage one HTN and stage two HTN, Odd Ratios: 4.555, 8.355 and 6.588 respectively. Overweight contributes to all stages of HTN by various degrees. Age is also a contributory factor for stage one HTN, stage two HTN and ISHTN.

Conclusion: Prevalence of different stages of HTN in Khartoum locality was high. Overweight contributes to all stages of HTN. Age and male sex were not contributing to pre-HTN and ISHTN respectively.

Alterations of Bronchial Cytokines in Bronchial Carcinoid Tumor Perioperatively

2021-07-30T04:28:36+00:00

As bronchial carcinoids are known to be notably rare, adequate histochemical investigations couldn’t have been carried out on these types of tumors hitherto. In this study, we investigated bronchial cytokines in a carcinoid tumor localized in the left main bronchus. Bronchial resection and reconstruction was performed without the lung resection. Bronchial lavage samples were obtained from both sides of main bronchial system preoperatively and postoperatively. TNF- α, IL- 8 and IL- 6 levels were measured by ELİSA. Preoperative TNF- α and IL- 8 levels were found to be 2-folds and 5-folds higher on the tumor side respectively (TNF- α; 14.184 pg/ml and IL- 8; 3359.86 pg/ml) compared to tumor-free bronchial system (TNF- α; 6.886 pg/ml, IL- 8; 615.072 pg/ml). Interestingly, both cytokine levels were found to be equal and within normal ranges on both sides subsequent to bronchial resection and reconstruction. There were no significant difference in IL- 6 levels between two bronchial systems preoperatively (IL- 6 levels of right bronchus, 16.44 pg/ml; levels of left bronchus, 19.11 pg/ml). However, there was more than four-fold increase in postoperative levels (IL- 6 level; 89.41 pg/ml). In this chapter, we found that preoperative TNF- α and IL- 8 levels were higher compared to the postoperative ones; whereas IL- 6 levels showed a significant increase, postoperatively. These findings led us through the idea that carcinoid tumors might be activating the inflammatory process among TNF- α and IL- 8 and the surgical bronchoplastic procedure could be the cause of enhanced IL-6 response.

History of Cautery: The Impact of Ancient Cultures

2021-07-30T04:43:49+00:00

Background: Healers around the world successfully practice traditional cautery (in Arabic kaiy) since ancient times. Traditional cautery, centuries of medical practice with unidentified exact origin has survived till today that authenticates its significance and effectiveness in mitigating human sufferings and diseases.

Objective: This overview aimed to describe and synthesise the literature on historical perspectives of traditional cautery.

Methods: The relevant literature published in English prior to 2018 was electronically searched in databases (PubMed, MEDLINE, Google Scholar, and OvidSP) using the Boolean operators and keywords. Manual searches and references of published articles and books were also conducted. A number of pertinent articles and abstracts (N=7490) were retained for extensive appraisal by two independent reviewers, and finally, 82 articles were included in this paper.

Results: The historical practice of traditional cautery is documented in diverse ancient cultures but the earliest references found in Surgical Papyrus (1550BC). The inconsistent data evidenced the origin of cautery, definitions, instruments, anatomical sites and techniques, advancements and research in traditional cautery since antiquity. Cautery was diminished in early 1800 century but revived in late 1800-1900 AD in the world. Presently, traditional cautery with better procedures and aseptic means is used by healers for treatment of a variety of diseases around the Eastern and Western world.

Conclusion: Traditional cautery has a checkered history and is a complementary modality for managing difficult-to-treat medical and surgical conditions. Scientifically more advanced modern types of cautery are used in the treatment of a variety of diseases across the world. This study calls for researching elucidating the underlying mechanisms of actions and effects of traditional cautery. Cautery is an ancient traditional therapy practised by healers across the globe since ancient times. Traditional cautery has checkered history, but most practitioners from diverse cultures of the world successfully practised it in the mitigation of human sufferings and diseases. Despite technological advancements in cauterisation techniques in modern medical sciences, traditional ancient cautery is survived due to a variety of strong socio-cultural beliefs and progressive safe application in selected patients not at risk of developing any complication. This historical overview calls for future studies to provide evidence-based data concerning the sociocultural factors, clinical perspectives and basic underlying mechanisms of action and effects of traditional cautery in different diseases.

Barriers to Implementation of Facility-based Kangaroo Mother Care for Pre-term and Low Birth Weight Infants in River Nile State, Sudan; 2014

2021-07-30T04:52:04+00:00

Background: Prematurity and low birth weight (LBW) currently account for approximately 40% of neonatal deaths in developing countries.

Objectives: To identify major factors that limit the introduction of kangaroo mother care (KMC) services in River Nile State, Sudan.

Methods: A facility based qualitative cross-sectional study conducted in two hospitals (Atbara and Al-Damar hospital). A total of seven pediatricians working in these two hospitals were interviewed using semi – structured interview.

Analysis: Analysis of the data was done manually. The interviewers' responses were entered into a data collection template. The data were reviewed and common themes were identified.

Results: Prematurity and low birth weight were a major health problem. Respiratory distress syndrome, hypothermia and sepsis were the leading causes of death. Problems facing pediatricians when caring for the preterm were; lack of incubators, non-functioning incubators, insufficient and untrained staff especially nurses beside rapid turnover. Only two of our pediatricians had heard about KMC but all of them were willing to adopt it in their units. Lack of awareness among mothers, health staff and the community, and the community health culture were the main two obstacles to KMC implementation. Financial support, staff training and isolated wards were needed for mothers' privacy. Knowledgeable practitioners to develop evidence-based policies were important for KMC implementation. Raising awareness among mothers, health cadre especially nurses caring for mothers and their babies and the community about KMC.

Conclusion: Lack of knowledge among health cadre, mother, families and community were obstacles to KMC. Awareness need to be raised.

Effect of Organotherapic Medicine on Glycaemia in Patients and Animals Receiving Antiretroviral Therapy

2021-07-30T04:56:18+00:00

Aims: To evaluate the effect of an organotherapic drug, produced from the pancreas of a young pig, on glycemic alterations in AIDS patients.

Methodology: Current study was carried out in a double-blind, placebo controlled and randomized design. AIDS patients who had high fasting glucose (>110 mg/dL) were selected so that the effect of the organotherapic drug could be evaluated. The patients were divided into two groups: Group I comprised patients who received the organotherapic drug diluted in 1x10¹² alcohol/ water 8%, once a day, with a sublingual-administered fasting dose of 10 drops, during four months. Group II consisted of patients receiving placebo once a day at the same dosage. Glucose oxidase method and ELISA, following the manufacturer’s instructions, respectively determined levels of glucose and insulin before treatment and monthly until four months after the start of treatment.

Results: Results registered hyperglycemia in 30% of the patients (60/200), higher than in the population at large (7-15%). This fact could be related to the time of infection (10.0±4.78 years) and treatment (9.3±3.76 years) of the patients. On the other hand, patients who underwent treatment with organotherapic medicine showed a significant reduction (p<0,001) in blood glucose levels (from 204.5±86.63 to 86.63±16) and lower insulin levels after four months of treatment (organotherapic group with 8.02±3.598 versus placebo with 23.83±3.670 p<0,001) within normality, regardless of age, time of infection and time of treatment. This fact suggests that the organotherapic drug was effective to stabilize blood glucose levels in patients.

Conclusion: Current study evidences that the organotherapic drug obtained from the pancreas of a young pig, diluted 1x10¹² in alcohol/ water 8% improves blood glucose levels in patients with hyperglycemia keeping within the normal range after four months of treatment. Considering the HAART therapy that significantly increases the life expectancy of AIDS patients but with significant metabolic alterations this study shows the possibility of utilization of complementary and alternative therapies. Although results indicate a significant effect of the organotherapic drug, additional studies are needed to evaluate the long-term effects.

Uterine Didelphys Pregnancy Management

2021-07-30T04:58:56+00:00

Introduction: Didelphys uterus is a rare Mullerian duct abnormality, which affects 1-3 in 3000 women worldwide. It is usually asymptomatic. There are many patients with this condition in Saudi Arabia, and this compelled us to study this condition.

Aims: To describe the management and outcomes of pregnant women diagnosed with uterus didelphys.

Study Design: This is a multicenter prospective cohort study.

Place and Duration of Study: This study was conducted in Saudi Arabia in 4 cities; 8 hospitals over a period of five years.

Methodology: 286 patients were enrolled in this study, all diagnosed previously to have didelphys uterus, pregnant and willing to join, follow up and deliver in one of the research hospitals. Patients consented to join the search and every 2 weeks follow up and management was done accordingly.

Results: 15 (5.2%) patients aborted during the first half of the pregnancy. 139 (48.6%) patients had cervical cerclage done. 79 (27.6) patients had preterm labor which was managed conservatively. 231 (80.8%) patients delivered by cesarean section and 17 (5.9%) delivered spontaneous vaginal delivery. Added to that, 38 (13.3%) had operative vaginal delivery. 271 neonates delivered. Unfortunately, three (1.1%) had intrauterine fetal death (IUFD) at 30-32 weeks of gestational age due to multiple congenital anomalies. All remaining neonates were normal and healthy except 25 (9.2%) who were admitted to NICU for various causes, but eventually discharged in good condition.

Conclusion: Antenatal care in patients with uterine didelphys is challenging, but given proper care, they can compete pregnancy with good neonatal outcome. Preterm labor and operative deliveries in the form of cesarean section and instrumental delivery were found to be high though.

Gaucher’s Disease: Prenatal and Post Natal Diagnostic Dilemma and Elucidating Case Series

2021-07-30T05:13:54+00:00

Gaucher’s Disease (GD) is a rare genetically inherited, autosomal recessive disorder. It is classified as a lysosomal storage disorder and is characterized by the accumulation of glycolipids. This is due to the deficiency of lysosomal hydrolase β – glucocerebrosidase. The gene responsible for synthesizing this enzyme is encoded by GBA1 on chromosome 1q21. The 3 clinical subtypes vary widely in their presentation. Moreover the presentation is not specific and mimics several other common and rare conditions. Having a child with GD poses severe psychological burden on the affected child and its family due to the associated morbidity and mortality. Appropriate prenatal diagnostic tests can provide sufficient information to prospective parents to take informed decisions. Case series and Literature Review is presented together with an objective to emphasize that a rare disease like GD can have bad prognosis and that prenatal diagnostics can help in the diagnosis of the disease during intrauterine life, to facilitate making a timely decision. It also highlights the importance of genetic counseling to avoid dismal outcomes. The case series also throw light on the challenges that GD presents in post natal life.

Preoperative Empyema can be a Cause of Cancel Bronchial Sleeve Resection for Lung Cancer?

2021-07-30T05:17:35+00:00

Surgical management of the cancer with empyema has rarely been reported in the literature because few of such cases are operable. Many patients might be misevaluated because of the incorrect staging associated with an acute or sub- acute infection. Even in the presence of an operable tumor mass; surgeons behave timid to these patients because of the possibility of infective postoperative complications. The balance between expected benefits and possible risk of surgical intervention is also important. If it is indicated, by the time pleural empyema is restored, procedures such as resection and even bronchoplasty should be performed. 59- years old patient the squamous cell carcinoma had completely obstructed left basal segments and caused to empyema. A thoracic catheter was inserted. Multiple pleural irrigations were done and proper antibiotherapy. Pathologic diagnosis of pleural fluid and pleural biopsy were benign. Pleural cultures were negative and amount of empyema fluid volume has decreased within two months. Positron emission tomography (PET) revealed a 2,5 cm sized left infrahilar tumor, right paratracheal, prevascular and subcarinal lymph nodes and non- homogeneous increased pleural activity. Mediastinal lymph nodes were evaluated as reactive with mediastinoscopy. Left lower lobectomy and lingulectomy were performed with bronchial resection and pathologic stage was 2A (T1bN1MO).

Sexually Transmitted Diseases Posing Health Hazards to Women Who Have Sex with Women

2021-07-30T05:28:23+00:00

Aims: The aim of this work is to present the findings of various studies relevant to the incidence of sexually transmitted disease (STD) among women who have sex with women (WSW). This being an important issue when considering the numerous and diverse types of infections possible.

Results: The various types of STD, vaginal infections, and abnormalities that are known among WSW includes: herpes simplex virus type 2, Chlamydia trachomatis, Neisseria gonorrhoeae, trichomoniasis, syphilis, hepatitis A, HIV, genital and oral human papillomavirus, pelvic inflammatory disease, allergic vaginitis, genital herpes and genital warts, squamous intraepithelial lesions, and bacterial vaginosis. Risk factors among WSW are the number of sexual partners, minimal use of protected sexual behaviors, and very low levels of knowledge of STD prevention among WSW. Drug-resistant pathogens have been observed in lesbian patients.

Conclusion: The threat of infection among WSW is significant, with the types and number of viral and bacterial potential pathogens being diverse and numerous. Recognition of risks will assist in correctly identifying the STD and aid in choosing the appropriate clinical care. Further research into the occurrence of STDs among WSW will benefit and contribute to public health.

Fatty Acid Composition and Antimicrobial Activity of Baphia massaiensis Seed Oil

2021-07-30T05:34:30+00:00

Aims: The seed oil composition of Baphia massaiensis seeds was determined using ¹H NMR and GC-MS techniques. The seed oil was also screened for antimicrobial activity.

Study Design: The study was designed to determine Baphia massaiensis seed oil fatty acid composition and antimicrobial activity.

Place and Duration of Study: Department of Chemistry, University of Botswana, between June 2012 and July 2014.

Methodology: The Baphia massaiensis seed cotyledons powder (29.2 g) were extracted by Soxhlet extraction using n-hexane/ 1-propanol. The seed oil (3.12 g) was esterified to FAMEs using dry methanol. The percentage composition of fatty acids methyl esters (FAMEs) in the seed oil of B. massaiensis was determined using ¹H NMR and GC-MS techniques. The antimicrobial screening was carried out using agar well diffusion method.

Results: The ¹H NMR method showed the oil composition to be 20% ω-3 fatty acids, 11% mono-unsaturated, 60% di-unsaturated and 9% saturated fatty acids. Based on GC-MC analysis, saturated fatty acids composition was 12.2% and unsaturated fatty acids were 87.8% of the total FAMEs. The major constituents of B. massaiensis seed oil FAMEs were linoleic acid (C_18:2; 49.0%) and linolenic acid (C_18:3; 36.7%) methyl esters. The FAMEs were active against E. coli, S. aureus and B. subtilis with 10-16 mm inhibition zones.

Conclusion: Linoleic acid (49.0%) and linolenic (36.7%) methyl esters were the major components of Baphia massaiensis FAMEs. The FAMEs were active against E. coli, S. aureus and B. subtilis showing 10-16 mm inhibition zone using agar well diffusion method.

Carcinosarcoma of Ovary, It’s Histopathological, Management and Prognostic Analysis with Review of Literature

2021-07-30T05:37:52+00:00

Carcinosarcoma is a mixed malignant biphasic tumour representing a rare entity and comprises of both epithelial and mesenchymal components. Primary ovarian carcinosarcoma is a rare neoplasm with a number of cases reported in the literature in the hundreds. It accounts for less than 1% of all ovarian tumours. These tumours are usually diagnosed at older age and advanced stage. It has aggressive clinical behaviour and survival depends on stage at presentation. Radiological imagings cannot differentiate carcinosarcomas from other ovarian cancers. Diagnosis is based upon histological findings. Cytoreductive debulking surgery is a crucial part in the treatment of carcinosarcoma of ovary. The role of adjuvant chemotherapy regimen is still controversial. Combination chemotherapy with taxane and platinum based regimen or ifosfamide and platinum based regimen are considered as adjuvant treatment. Despite aggressive treatment modalities such as surgery and chemotherapy, the outcome is poor. Response to therapy and overall survival for carcinosarcoma are poor in comparison to that of epithelial ovarian malignancies. Due to rarity of the disease, such poor prognosis needs collaboration of studies with molecular analysis to obtain new therapeutic guidelines to improve survival of the patients.

Novel Structures of Uracil Mustard (Uramustine) Retaining Cytotoxic Activity and Drug-likeness for Oral Administration

2021-07-30T05:42:52+00:00

Aims: To present 12 new variants of uracil mustard having drug-like properties and cytotoxic functional group, by utilizing uracil mustard (uramustine) as a lead compound. Utilize rigorous substructure and similarity of a molecular scaffold to determine drug like variants. Physicochemical properties determined indicate the variants have favorable drug-likeness.

Study Design: Conduct molecular database search utilizing features of substructure and similarity based upon uracil mustard.

Place and Duration of Study: Department of Chemistry, Medicinal Chemistry Study Section, University of Nebraska at Omaha, Omaha Nebraska between January 2015 to March 2015.

Methodology: Uracil mustard consists of the pyrimidine derivative uracil, having the bifunctional nitrogen mustard cytotoxic moiety covalently bonded onto the ring. A systematic search, utilizing substructure component and similarity, within an in-silico database search successfully determined 12 variants. Rigorous criteria for drug-likeness were implemented to screen potential candidates that included the application of the Rule of 5. In addition, maintaining the cytotoxic moiety of nitrogen mustard was crucial.

Results: A total of 12 variants of uracil mustard was identified after an extensive molecular database search using rigorous criteria. All 12 variants, and including uracil mustard, showed zero violations of the Rule of 5, thereby indicating favorable drug-likeness. Values of polar surface area for all compounds at less than 80 Angstroms² are suitable for central nervous system penetration. Polar surface area, number of atoms, and Log P for all compounds increased as the molecular weight increases. Structure substituents include nitrogen mustard groups, hydroxyl, alkyl and carbonyl moieties. Cluster analysis discerned greatest similarity among members of this group.

Conclusion: Applying rigorous search criteria within a molecular data base, for comparison and reject, successfully identified 12 variants of uracil mustard that show favorable drug-likeness in addition to cytotoxic capability. The design of new antitumor agents is important for increasing efficacy of the clinical treatment of cancer. Variation of physicochemical properties can benefit the efficacy of anticancer drugs and should be further investigated for the benefit of patients.