Hematological, clinical, cytogenetic and molecular profiles of confirmed chronic myeloid leukemia patients at presentation at a tertiary care teaching hospital in Addis Ababa, Ethiopia: a cross-sectional study.

BACKGROUND: In low-income countries there is insufficient evidence on hematological, clinical, cytogenetic and molecular profiles among new CML patients. Therefore, we performed this study among newly confirmed CML patients at Tikur Anbesa Specialized Hospital (TASH), Ethiopia. OBJECTIVE: To determine the hematological, clinical, cytogenetic and molecular profiles of confirmed CML patients at tertiary care teaching hospital in Addis Ababa, Ethiopia. METHODS: A facility-based cross-sectional study was conducted to evaluate hematological, clinical, cytogenetic and molecular profiles of confirmed CML patients at TASH from August 2021 to December 2022. A structured questionnaire was used to collect the patients' sociodemographic information, medical history and physical examination, and blood samples were also collected for hematological, cytogenetic and molecular tests. Descriptive statistics were used to analyze the sociodemographic, hematological, clinical, cytogenetic and molecular profiles of the study participants. RESULTS: A total of 251 confirmed new CML patients were recruited for the study. The majority of patients were male (151 [60.2%]; chronic (CP) CML, 213 [84.7%]; and had a median age of 36 years. The median (IQR) WBC, RBC, HGB and PLT counts were 217.7 (155.62-307.4) x103/µL, 3.2 (2.72-3.6) x106/µL, 9.3 (8.2-11) g/dl and 324 (211-499) x 103/µL, respectively. All patients had leukocytosis, and 92.8%, 95.6% and 99.2% of the patients developed anemia, hyperleukocytosis and neutrophilia, respectively. Fatigue, abdominal pain, splenomegaly and weight loss were the common signs and symptoms observed among CML patients. Approximately 86.1% of the study participants were Philadelphia chromosome positive (Ph+) according to fluorescence in situ hybridization (FISH). P210, the major breakpoint protein, transcript was detected by both qualitative polymerase chain reaction (PCR) and quantitative real time polymerase chain reaction (PCR). CONCLUSION: During presentation, most CML patients presented with hyperleukocytosis, neutrophilia and anemia at TASH, Addis Ababa. Fatigue, abdominal pain, splenomegaly and weight loss were the most common signs and symptoms observed in the CML patients. Most CML patients were diagnosed by FISH, and p120 was detected in all CML patients diagnosed by PCR. The majority of CML patients arrive at referral center with advanced signs and symptoms, so better to decentralize the service to peripheral health facilities.

Prenatal developmental toxicity study of herbal tea of Moringa stenopetala and Mentha spicata leaves formulation in Wistar rats.

Background: Moringa stenopetala and Mentha spicata have long been used to treat diabetes, hypertension, asthma, and other ailments. Herbal tea of M. stenopetala and Mentha spicata leaves formulation showed better antidiabetic and antihypertensive activities. This study investigated the prenatal developmental toxicity potential of the herbal tea of M. stenopetala and M. spicata leaves blend in rats. Methods: Wistar pregnant rats were randomly distributed into four groups (n = 8). Group I (control) dams received distilled water. Group II-IV dams were treated with 559.36, 1118.72, and 2237.44 mg/kg of herbal tea of M. stenopetala and Mentha spicata leaves formulations, respectively, during days 5-19 of gestation. Maternal mortality, clinical signs, body weight changes, and food consumption were recorded. On gestation day 20, cesarean sections were performed, and maternal parameters of systemic toxicity (e.g., body weight, serum biochemistry, organ weight, and macro-pathology) as well as reproductive toxicity (e.g., number of corpora lutea, implantations, resorptions (early/late), pre/postimplantation losses, number of fetuses (live/dead), and fetal body weights, length, and their sex ratio) were evaluated. Fetuses were further examined for external, soft tissue, and skeletal alterations. Results: No herbal tea-related maternal deaths or overt toxic symptoms were observed. The measured maternal systemic and reproductive toxicity parameters showed no herbal tea-associated significant alterations at any dosage levels. Moreover, there were no overt toxic effects of the herbal tea on the fetal external, visceral, or skeletal prenatal growth and development. Conclusion: The study findings demonstrated that the herbal tea of M. stenopetala and M. spicata leaves blend could be relatively safe/low toxic to pregnant rats and developing fetuses. The no-observed-adverse-effect level (NOAEL) of herbal tea for maternal toxicity, fetotoxicity, and teratogenicity in rats is estimated to be > 2237.44 mg/kg/day.

Reference Intervals for Absolute and Percentage CD4+ T Lymphocytes among an Apparently Healthy Population in Addis Ababa, Ethiopia.

Background: Reference intervals for clinical laboratory parameters differ based on several factors, including age, sex, genetic variation, and geographic location. This variation influences clinical decisions and treatment monitoring. Currently, Ethiopia has used adopted reference intervals from manufacturer values derived from non-Africans. Therefore, the aim this study was to determine reference intervals for absolute and percentage CD4+ T cells for an apparently healthy population in Addis Ababa, Ethiopia. Methods: A community-based cross-sectional study was conducted on 361 apparently healthy people in four subcities in Addis Ababa from January to June 2019. Sociodemographic and clinical data were collected using a structured questionnaire after informed consent had been obtained. Blood samples were collected and CD4+ T-lymphocyte enumeration performed using a BD FACSPresto near-patient CD4 counter. Data were entered and analyzed using SPSS 20. Reference intervals were determined by a nonparametric test estimating percentiles 2.5 (lower limit) and 97.5 (upper limit) with 95% CIs. P<0.05 was considered statistically significant. Results: A total of 337 (183 female and 154 male) healthy participants of median age 28 (IQR 17-35) years were included in the final analysis. Medians of absolute and percentage CD4+ T-cell counts (932.0 and 42.9, respectively) of female participants were significantly higher than male participants (802.5 and 38.7, respectively; P<0.05). Reference intervals for absolute CD4+ T-cell count and percentages in males were 483.8-1,310 cells/µL and 18.1-57.3 and in females 447.8-1,479.8 cells/µL and 25.6-58.9, respectively. Conclusion: The CD4+ T-count reference intervals established in this study showed some inconsistency from the manufacturer's provided values and other studies and also revealed sex differences, necessitating sex-specific locally established reference intervals.

Composition of the Essential Oil Thymus schimperi and Evaluation of Its Acute and Subacute Toxicity in Wistar Albino Rats: In Silico Toxicity Studies.

BACKGROUND: In Ethiopian traditional medicine, the aerial part of Thymus schimperi is widely used to treat diseases such as gonorrhea, cough, liver disease, kidney disease, hypertension, stomach pain, and fungal skin infections. However, there is insufficient investigation on the toxic effect of the essential oil of T. schimperi. The aim of this study was, therefore, to evaluate the acute, subacute, and in silico toxicity of Thymus schimperi essential oil in the Wistar albino rats. METHOD: Essential oil of the aerial part of T. schimperi extracted by hydrodistillation was analyzed by GC-MS. The oil was subjected to toxicity studies. In the acute toxicity study, rats were randomly divided into seven groups (n = 5). The control group received only distilled water with 2% of tween 80, whereas the experimental groups received single doses of 300, 600, 900, 1200, 1500, and 2 000 mg/kg of the oil. In the subacute toxicity study, rats were randomly divided into four groups (n = 10). The control group received distilled water with 2% of tween 80, whereas the experimental groups received 65 mg/kg, 130 mg/kg, and 260 mg/kg of the oil orally for 28 days. At the end of the experiment, blood samples were collected for hematology and clinical chemistry evaluation. Gross pathology and histopathology of the liver and the kidneys were also evaluated. For the in silico toxicity study, PubChem CID numbers of GC-MS identified bioactive compounds in the essential oil of T. schimperi obtained from PubChem. Chemdraw (8.0) was used to construct two-dimensional structures of the compounds. The Swiss ADMET web tool was used to convert the two-dimensional structures into a simplified molecular-input line input system (SMILES). In addition, the toxicity parameters were predicted via vNN and ADMET servers. RESULTS: In this study, the LD50 of the essential oil of T. schimperi was found to be 1284.2 mg/kg. According to the World Health Organization, the oil is classified as moderately hazardous in its oral administration. In the subacute toxicity study, rats showed no significant changes in behavioral indices, gross pathology, body weight, biochemical, and most hematological parameters. However, hematological profiles showed a significant decrement in WBC counts and a significant increment of MCV in high dose (260 mg/kg) groups as compared to the control group. Furthermore, no significant differences were observed between the control and essential oil-treated groups, observed in the gross histopathology of the liver and the kidneys. In the in silico toxicity study, all compounds derived from the essential oil showed no cardiac toxicity (h-ERG Blocker), AMES (Ames Mutagenicity), and cytotoxicity via ADMET and vNN-ADMET toxicity predictors. However, by using these servers, about 8.6% of the compounds showed hepatotoxicity, only 3.45% caused drug-induced liver injury, and only 1.75% were potentially toxic to the mitochondrial membrane. CONCLUSION: From the results of this study, oral administration of the essential oil T. schimperi up to a dose of 130 mg/kg is not harmful. However, in the high-dose (260 mg/kg) group, the WBC count was significantly decreased and the MCV was significantly increased. In the in silico toxicity study, most of the components of the oil were found to be nontoxic, although a few of the compounds showed hepatotoxicity and mitochondrial membrane potential toxicity. It is, therefore, essential to conduct chronic toxicity of the essential oil as well as its components, which showed toxicity in the in silico study before using preparations containing the essential oil of T. schimperi.