Novel Structures of Uracil Mustard (Uramustine) Retaining Cytotoxic Activity and Drug-likeness for Oral Administration | Chapter 16 | New Insights into Disease and Pathogen Research Vol. 2

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.

Author(s) Details

Dr. Ronald Bartzatt
Durham Science Center, University of Nebraska, 6001 Dodge Street, Omaha, Nebraska 68182, USA.

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Carcinosarcoma of Ovary, It’s Histopathological, Management and Prognostic Analysis with Review of Literature | Chapter 15 | New Insights into Disease and Pathogen Research Vol. 2

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.

Author(s) Details

Dr. Priyanka Priyadarshini
Department of Obstetrics and Gynaecology, Calcutta National Medical College and Hospital, Kolkata, West Bengal, 700014, India.

Dr. Tapan Kumar Sahoo
Department of Radiotherapy, Acharya Harihara Regional Cancer Centre, Cuttack, Odisha, 753007, India.

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Fatty Acid Composition and Antimicrobial Activity of Baphia massaiensis Seed Oil | Chapter 14 | New Insights into Disease and Pathogen Research Vol. 2

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.

Author(s) Details

Dr. Ngonye Keroletswe
University of Botswana, Gaborone, Botswana and Botswana Institute for Technology Research and Innovation, Gaborone, Botswana.

Dr. Ofentse Mazimba
Botswana International University of Science and Technology, Palapye, Botswana.

Prof. Runner R. T. Majinda
University of Botswana, Gaborone, Botswana.

Prof. Ishmael Masesane
University of Botswana, Gaborone, Botswana.

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Sexually Transmitted Diseases Posing Health Hazards to Women Who Have Sex with Women | Chapter 13 | New Insights into Disease and Pathogen Research Vol. 2

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.

Author(s) Details

Dr. Ronald Bartzatt
Durham Science Center, University of Nebraska, 6001 Dodge Street, Omaha, Nebraska 68182, USA.

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Preoperative Empyema can be a Cause of Cancel Bronchial Sleeve Resection for Lung Cancer? | Chapter 12 | New Insights into Disease and Pathogen Research Vol. 2

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).

Author(s) Details

Nilgün Kanlıoğlu Kuman
Department of Thoracic Surgery, Faculty of Medicine, Adnan Menderes University, Aydın, Turkey.

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Gaucher’s Disease: Prenatal and Post Natal Diagnostic Dilemma and Elucidating Case Series | Chapter 11 | New Insights into Disease and Pathogen Research Vol. 2

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.

Author(s) Details

Dr. Mohammed Ismail Khan
Department of Obstetrics and Gynaecology (Academic), ESIC Medical College and Hospital, Sanathnagar, Hyderabad, India.

Dr. Swathi Emmadisetty
Department of Obstetrics and Gynaecology, ESIC Medical College and Hospital, Sanathnagar, Hyderabad, India.

Dr. Asna Yasmeen
Mesco College of Pharmacy, Mustaidpura, Hyderabad, India.

Dr. Shahzeb Zaman
Department of Anaesthesiology, Shadan Institute of Medical Sciences, Peerancheru, Hyderabad, India.

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Uterine Didelphys Pregnancy Management | Chapter 10 | New Insights into Disease and Pathogen Research Vol. 2

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.

Author(s) Details

Dr. Mohammad Othman
Department of Obstetrics and Gynecology, Faculty of Medicine, Al-Baha University, Saudi Arabia.

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Effect of Organotherapic Medicine on Glycaemia in Patients and Animals Receiving Antiretroviral Therapy | Chapter 09 | New Insights into Disease and Pathogen Research Vol. 2

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 1×1012 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 1×1012 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.

Author(s) Details

A. R. T. Pupulin
Department of Basic Health Sciences, State University of Maringa, Maringa, Brazil.

L. Mortean
Department of Basic Health Sciences, State University of Maringa, Maringa, Brazil.

T. Sakurada Jr
Department of Basic Health Sciences, State University of Maringa, Maringa, Brazil.

M. Spack Jr
Department of Basic Health Sciences, State University of Maringa, Maringa, Brazil.

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Barriers to Implementation of Facility-based Kangaroo Mother Care for Pre-term and Low Birth Weight Infants in River Nile State, Sudan; 2014 | Chapter 08 | New Insights into Disease and Pathogen Research Vol. 2

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.

Author(s) Details

Dr. Asma Abdelaal Abdalla
Department of Community Medicine, Faculty of Medicine, University of Khartoum, Sudan.

Dr. Eman Aljaali Hamid Muhammed Ali
Department of Community Medicine, Faculty of Medicine, University of Khartoum, Sudan.

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History of Cautery: The Impact of Ancient Cultures | Chapter 07 | New Insights into Disease and Pathogen Research Vol. 2

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.

Author(s) Details

Naseem A. Qureshi
National Center for Complementary and Alternative Medicine, Ministry of Health, Riyadh, Kingdom of Saudi Arabia.

Saud M. Alsanad
College of Medicine, Imam Muhammad Ibn Saud Islamic University (IMSIU), Riyadh, Kingdom of Saudi Arabia.

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