Clinical Chemistry Examinations Research Articles

Dose Range-Finding Toxicity Study in Rats With Recombinant Human Lactoferrin Produced in Komagataella phaffii.

The oral toxicity of recombinant human lactoferrin (rhLF, Helaina rhLF, Effera™) produced in Komagataella phaffii was investigated in adult Sprague Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3-6 rats/sex/dose. The vehicle control group received sodium citrate buffer, and the test groups received daily doses of 200, 1000, and 2000mg of rhLF in sodium citrate buffer per kg body weight. Bovine LF at 2000mg/kg body weight per day was used as a comparative control. Clinical observations, body weight, hematology, clinical chemistry, iron parameters, immunophenotyping, and gross examination at necropsy were used as criteria for detecting the effects of treatment in all groups and to help select dose levels for future toxicology studies. Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14days was well tolerated in rats at levels up to 2000mg/kg/day, or 57 × Helaina's intended commercial use in adults, and indicating that a high dose of 2000mg/kg/day is appropriate for future definitive toxicology studies.

Studi filariasis berbasis pemeriksaan laboratorium di Kota Semarang

Background: Filariasis is a disease caused by parasitic nematodes of Filariae. Filariasis is caused by filarial worm species, namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. This disease is transmitted through the bite of infected mosquitoes (Anopheles, Aedes, and Culex). Symptoms of filariasis in men or women include damage to the lymphatic system swelling of the arms, legs, and genitals, which causes pain, decreased productivity, and social problems. Filarial diagnosis through examination of blood smears to detect filarial parasites in the blood, accompanied by hematological and clinical chemical examinationsObjective: This study aimed to describe filariasis through blood tests (blood smears, hematological examinations, and clinical chemistry examinations) on filariasis respondents using a cross-sectional approach.Method: This type of descriptive research uses a cross-sectional approach. The research subjects were 6 filarial respondents in Pedurungan District, Semarang City. The examination was conducted at the Tologosari Wetan and Kulon Health Centers on September 12-18, 2020. Secondary data collection was obtained from capillary blood examination using thin blood smears, automatic hematological examination using a hematology analyzer, and clinical chemistry examination using the spectrophotometer method with a spectrophotometer. The research data was processed and analyzed using Univariate analysis using maximum, minimum, and average values.Results: Hematological examination for hemoglobin level of 12,5 g%, leukocytes 3200 cells/ml, platelets 137.00 cells, erythrocytes 4,07x106 cells, lymphocytes 35 cells, neutrophils 73 cells, eosinophils 1 cell, monocytes 9 cells, MCH 30,78 pg, MCV 86,48 fl, MCHC 36,24 g/l and clinical chemistry examination results for cholesterol 145,7 g/dl and triglycerides 104,6 g/dl. Meanwhile, on examination of thin blood smears, microfilariae were found.Conclusion: The results of the blood smear evaluation showed an abnormality in the size of the red blood cells in the form of microcytic (smaller red blood cell size), and filarial findings were found. In contrast, hematology and clinical chemistry examination results obtained normal results.

CRITICAL VALUE OF GLUCOSE USING CRITIVA 1.0 APPLICATION IN BALI MANDARA EYE HOSPITAL

Critical value is very critical result in laboratory examination that can indication several emergency conditions. Reporting critical values are controversial between hospital management, clinicians, and laboratory. Reporting critical value required effective communication. Information technology has become one of the solution effective communication in reporting critical values. Critical values can occur in clinical chemistry, hematology, and other laboratory examination. Glucose is one of the clinical chemistry parameters which is often foound critical value and therapy must be given immediately. Aim of this research is to evaluated time reporting using Critiva 1.0 application in cellular phone of clinical pathologist Bali Mandara Eye Hospital. Samples were 50 times reporting the glucose critical value simulation using the Critiva 1.0 application and 50 times reporting the Standard Operating Operations (SPO) simulation at the Bali Mandara Eye Hospital. Simulation carried by laboratory techonology in charge. We used means to analyze time reporting and SPSS version 16. Mean reporting glucose critical value using Critiva 1.0 application was 12 seconds. Mean reporting glucose critical value using SPO Bali Mandara Eye Hospital was 720 seconds.

Evaluation of genotoxicity and 13-week subchronic toxicity of root of Asarum heterotropoides var. seoulense (Nakai) Kitag

Ethnopharmacological relevanceAsarum heterotropoides var. seoulense (Nakai) Kitag is a traditional herbal medicine used in Korea and China. It is effective in aphthous stomatitis, local anesthesia, headache, toothache, gingivitis, and inflammatory diseases. However, information on the toxicity of the root of Asarum heterotropoides var. seoulense (Nakai) Kitag (AR) is limited. Therefore, preclinical toxicity studies on AR are needed to reduce the risk of excessive intake. Aim of the studyWe aimed to evaluate genotoxicity and the potential toxicity due to repeated administration of AR powder. Materials and methodsIn vitro bacterial reverse mutation assay (Ames), in vitro chromosomal aberration assay (CA), and in vivo micronucleus (MN) assay in ICR mice were conducted. As positive results were obtained in Ames and CA assays, alkaline comet assay and pig-a gene mutation test were conducted for confirmation. For evaluating the general toxicity of AR powder, a 13-week subchronic toxicity test was conducted, after determining the dose by performing a single and a 4-week dose range finding (DRF) test. A total of 152 Sprague-Dawley (SD) rats were orally administered AR powder at doses of 0, 150, 350, 500, 1000, and 2000 mg/kg/day in the 13-week subchronic toxicity test. Hematology, clinical chemistry, urinalysis, organ weight, macro-, and microscopic examination were conducted after rat necropsy. ResultsAR powder induced genotoxicity evidenced in the Ames test at 187.5, 750, 375, and 1500 μg/plate of TA100, TA98, TA1537, and E. coli WP2uvrA in the presence and absence of S9, respectively; CA test at 790 μg/mL for 6 h in the presence of S-9; 75 μg/mL for 6 h in the absence of S-9, and 70 μg/mL for 22 h in the absence of S-9 in the stomach in the comet assay but not in MN and pig-a assays. In the 13-week subchronic toxicity study, clinical signs including irregular respiration, noisy respiration, salivation, and decreased body weight or food consumption were observed in males and females in the 2000 mg/kg/day group. In hematology tests, clinical chemistry, urinalysis, organ weight, and macroscopic examination, changes were observed in the dose groups of 500 mg/kg/day and above. Microscopic examination revealed hyperplasia of the stomach as a test-related change. Hepatocellular adenoma and changes in liver-related clinical chemistry parameters were observed. The rat No Observed Adverse Effect Level (NOAEL) was 150 mg/kg/day in males and <150 mg/kg/day in females. ConclusionsAR powder is potentially toxic to the liver and stomach and should be used with caution in humans. A long-term study on carcinogenicity is necessitated because DNA damage or changes in tissue lesions were observed in SD rats.

Evaluation of serum markers of the immune response and bone metabolism facilitates early detection of psoriatic arthritis in patients with psoriasis

Relevance: Psoriatic arthritis (PA) is a severe complication of psoriasis, leading to progressive damage to the musculoskeletal system, a decrease in the quality of life and early disability. CASPAR criteria, widely used for PA diagnosis, are highly sensitive and specific. However, some patients with psoriasis score 3 with CASPAR criteria without an established PA diagnosis. At present, there is a search for PA biomarkers, which could mirror the stages of pathogenesis of joint and enthesis destruction in this disease.&#x0D; Aim: To identify the most significant changes in biochemical parameters in patients with PA, that would be pathophysiologically associated with the disease.&#x0D; Materials and methods: We performed an open label comparative parallel groupstudy in 60 patients with PA and 40 patients with psoriasis without PA. Clinical assessments included filling in the questionnaires, past history, dermatologist consultation, severity of psoriasis by PASI, and PA activity. Clinical chemistry examination included the levels of antibodies to citrullinated peptide, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen HLA B27, immunoglobulins A, M, and G, complement system components C3, C4, circulating immune complexes (CIC), as well as bone metabolism parameters (calcium, phosphorus, magnesium, seromucoid, alkaline phosphatase (AP), osteocalcin, parathyroid hormone, vitamin D, matrix metalloproteinases MMP-1, MMP-3, MMP-8, and cartilage oligomeric matrix protein (СОМР).&#x0D; Results: Psoriasis was diagnosed in 86.6% (n=52) of the patients with PA. Family history of psoriasis was confirmed in 55.0% (n=22) of the patients with psoriasis without PA and in 60.0% (n=36) of the patients with PA (p=0.681). Compared to the patients with psoriasis without PA, the patients with PA had higher prevalence of psoriatic onychodystrophy (71.6%, n=43, vs. 35.0%, n=14, p=0.0004), dactylitis (28.3%, n=17, vs. 5.0%, n=2, p=0.004), extra-articular bone proliferation signs (26.6%, n=16, vs. 5.0%, n=2, p=0.006). In the patients with PA, compared to those without PA, there was a significant increase in CRPlevels (27.4 vs. 9.5 mg/l, p=0.002), more than 2-fold increase in IgM and IgG (IgM, 2.35 vs. 1.2 g/l, p=0.023; IgG, 17.7 vs. 8.45 g/l, p 0.0001), and CIC (89.3 vs. 29.5 mU/ml, p=0.0003). Serum phosphorus and magnesium levels in the patients with PA were lower than in the psoriasis patients without PA (phosphorus 0.8 vs. 1.6 mmol/l, respectively, p=0.045, magnesium 0.5 vs. 1.0 mmol/l, respectively, p=0.001), with somewhat higher parathyroid hormone levels (67.3 vs. 25.1 ng/ml, respectively, p=0.013). Osteocalcin levels in the PA patients were by 37.3% lower than in the patients with psoriasis without PA (17.57 vs. 24.13 ng/ml, respectively, p=0.004). MMP-1 levels in the PA groupwere 12.3-fold higher than in the non-PA group(37.68 vs. 3.05 ng/ml, respectively, p 0.0001), and MMP-3 levels were 3.7-fold higher (42.35 vs. 11.36 ng/ml, respectively, p=0.022). In the patients with PA, APlevels were 2.52-fold higher than in the control group(150.2 vs. 59.5 U/ml, respectively, p=0.007), and COMPlevels were 2.08-fold higher (415.2 vs. 199.5 ng/ml, respectively, p=0.006).&#x0D; Conclusion: The patients with PA have higher serum CRP, IgM, IgG, CIC, MMP-1, MMP-3, AP, and COMPlevels and lower osteocalcin, phosphorus, and magnesium concentrations, than the patients with psoriasis. These parameters are not PA-specific; however, the search for the most sensitive biomarkers of the systemic immune response and bone remodeling seems to be a promising area of research, since identification of such markers would allow for timely prediction and detection of PA in patients with psoriasis.

Hematological and biochemical effects of Toxoplasma gondii, Entamoeba histolytica, and Schistosoma infection among Hepatitis C virus patients from Menoufia Province, Egypt

Background: Hepatitis C virus (HCV) is highly distributed in Egypt. Moreover, parasitic diseases such as schistosomiasis, toxoplasmosis, or amebiasis are frequent in Egypt. Dual infections of HCV and each of these parasitic diseases are possible and associated with bad clinical consequences. The present study was done to monitor the clinical, biochemical, and hematological changes in Toxoplasma gondii, Entamoeba histolytica, and/or Schistosoma co-infection in the HCV-infected patients from Menoufia Province, Egypt. Methods: One hundred and nine blood samples, HCV monoinfected patients and co-infected with T. gondii, E. histolytica, and/or Schistosoma, were monitored and subjected to clinical chemistry and hematological examinations Results: Liver cirrhosis in patients with concomitant multiple parasites during chronic HCV infections showed a high percentage compared to HCV mono-infected patients. Moreover, significant increases in the level of alpha-fetoprotein, aspartate transaminase, prothrombin time, and the relative monocyte count were demonstrated in patients with concomitant multiple parasites during chronic HCV infections compared to HCV mono-infected patients. Changes in the levels of platelets and relative lymphocytes/neutrophils count were detected during dual or multiple infections. Conclusions: Schistosomiasis, toxoplasmosis, or amebiasis had unpropitious effects on HCV-infected patients and it is recommended to screen these parasitic diseases among HCV patients to reduce the HCV clinical outcome.

Nonclinical safety evaluation of oral recombinant anti-human papilloma virus vaccine (RHPV 16 & 18): Regulatory toxicology studies in mice, rats and rabbits – An innovative approach

AimThe human papilloma virus (HPV) type 16 and 18 causes nearly 70% of uterine cervical cancers. Oral administration of live Salmonella typhi Ty21a, expressing major capsid proteins (L1) of HPV 16 and 18 is a potential choice for immunization in adolescent girls under low resource settings. Present study aimed to assess the nonclinical safety of recombinant S. typhi expressing HPV 16 and 18 (rStHPV) proteins. MethodologyThe acute toxicity of rStHPV was tested by intranasal single dose administration, of 10 and 50 folds higher than clinical prophylactic dose, in mice and rat followed by monitoring their survival for 14 days. Sub-chronic toxicity was evaluated in rats and rabbits with prophylactic and 5 times (average) to clinical prophylactic dosages on scheduled days (1st, 3rd & 5th day) through oral and intranasal routes. The immune/allergic response of rStHPV was assessed in mice through intranasal and intra-peritoneal routes. Experimental animals were daily monitored for live phase, and clinical chemistry, haematology, immunotoxicology, immunogenic response and histopathological examination of vital organs on 15th, 29th and 93rd days. ResultsNo abnormal changes were noticed in live phase activity, clinical chemistry and haematology profile. The gross necropsy, organ weights and histopathology were found to be normal. No immunotoxicity was recorded as evaluated by tier I tests. Allergic immune response, as evaluated with IgE levels was also negative irrespective of test routes. On the other hand, a significant (P < 0.01) increase of anti-HPV IgG levels was noted in mice exposed through intranasal route. Though the pre-terminal mortality was noted in mice (6–15%), rats (10%) and rabbits (15%), the autopsy revealed no signs of toxicity related to rStHPV, as the changes neither significant nor dose dependent; and even noted in vehicle control also. ConclusionThe study results suggested ‘no observable adverse effects’ of rStHPV even at higher dosages (5, 10 & 50 folds) than intended clinical dose. A significant increase of anti-HPV specific IgG suggests the immunogenicity of vaccine. The innovative approach of current study is nonclinical toxicology evaluation of vaccine through intra-nasal route, an alternate route apart from stipulated regulatory guidelines.

14-Day Repeated Intraperitoneal Toxicity Test of Ivermectin Microemulsion Injection in Wistar Rats.

To evaluate the safety of ivermectin microemulsion injection, 100 Wistar rats were injected intraperitoneally at 0.38 g/kg, 0.19 g/kg, and 0.1 g/kg for 14 days. The 14-day repeated toxicity test of ivermectin microemulsion injection was systematically evaluated by clinical observation, organ coefficient, hematological examination, clinical chemistry examination, and histopathological examination. The results showed that no rats died during the test. At the initial stage of treatment, the rats in the high dose group had mild clinical reaction, which disappeared after 4 days. Clinical chemistry showed that the high dose of ivermectin microemulsion could cause significant changes in ALT and LDH parameters in male rats; high and medium doses could increase the liver coefficients of male and female rats. The toxic target organ may be the liver as indicated by histopathological findings. No significant toxic injury was found in the heart, liver, spleen, lung, kidney, brain, ovary, and testes of all groups of rats. No drug-related toxic effects were found at low doses, and thus the NOVEL of ivermectin microemulsion injection was 0.19 g/kg.

A Comprehensive Toxicological Assessment of Fulvic Acid.

Fulvic acid (FA), a humic substance, has several nutraceutical properties, including anti-inflammation, antimicrobial, and immune regulation abilities. However, systematic safety assessment remains insufficient. In the present study, a battery of toxicological studies was conducted per internationally accepted standards to investigate the genotoxicity and repeated-dose oral toxicity of FA. Sprague-Dawley (SD) rats or ICR mice were used. Compared to the control group, there were no significant changes (all p > 0.05) in all FA treatment groups in the bacterial reverse mutation test, in vitro mammalian chromosome aberration test, in vivo sperm shape abnormality assay, and in vivo mouse micronucleus assay. The acute toxicity test showed that no mortality or toxic effect was observed following oral administration of the maximum dose of 5,000 mg/kg BW/day to mice or rats. A 60-day subchronic study was conducted at 0 (control), 200, 1,000, and 5,000 mg/kg/day. Compared to the control group, there were no significant changes (all p > 0.05) in the body weights, feed consumption, clinical signs, hematology, clinical chemistry, organ weights, or histopathology examinations. In conclusion, the no-observed-adverse-effect-level (NOAEL) of FA supplementation from the 60-day study was determined to be 5,000 mg/kg body weight/day, the highest dose tested. Our findings suggest that the oral administration of FA may have higher safety.

Turnaround time for common clinical chemistry examinations and root cause analysis for its delay

Objectives: Measurement of turnaround time for common clinical chemistry examinations and performing root cause analysis for causes for inadequate turnaround time for examinations. Materials and Methods: The Turnaround Times (TAT) of common biochemistry tests ordered by physicians for OPD, IPD and ICU patients were evaluated. Various time periods were recorded, calculated and evaluated. Root cause analysis for delay in TAT was performed by Ishikawa fishbone method. Results and Conclusions: The study shows that average TAT for OPD patients was 22-23 hours, for indoor patient was 6-7 hours and for ICU patient was 7-8 hours. There was major contribution of report transport system in the total TAT, while actual analytical TAT contributed very small to over all TAT. The study shows that, lack of efficient sample and report transport, lack of man power and lack of electronic transport of report is root cause of delay in TAT. Keywords: Turnaround time, Root cause analysis, Ishikawa fishbone method.

Exploration and practice of the combination of pluralistic teaching and process assessment in the clinical biochemical teaching

Clinical biochemical examination is an important part of medical laboratory, and it is also the key and difficult point of all kinds of examinations.However,the teaching of clinical biochemistry is easily to enter the misunderstanding of focusing only on the instrument operation, while others depend on self-study. There is even confusion that teachers don′t know what to teach and students don′t know what to learn.In this paper, the teaching experience of the clinical biochemical laboratory is described,formulated a scientific block training program, adopted the teaching mode of combining tutorial responsibility with daily teaching,flexibly used a variety of teaching methods and procedural examinations, and greatly improved the teaching quality. Key words: Clinical chemistry examination; Standardized training of residents; Clinical teaching

Anaplasma bovis infection in a horse: First clinical report and molecular analysis

A 23-year-old male Thoroughbred horse at the Korean Military Academy appeared thin with visible rib bones and presented clinical signs of fever, anorexia, lethargy, and severe dehydration. To determine the presence of various febrile disease-causing agents, the 23 cohabiting horses at the academy, including this horse, were subjected to hematology, blood chemistry, and molecular analysis using whole blood samples collected during regular medical check-ups. On the basis of clinical history, physical examination, hematology, blood chemistry, and fecal examination, differential diagnosis using molecular analyses was performed for various febrile disease-causing agents, including Lyme borreliae, Coxiella, piroplasms (Babesia and Theileria), Rickettsiales (Anaplasma, Ehrlichia, and Rickettsia), equine herpesvirus, equine infectious anemia virus, and equine arteritis virus. While other pathogens were not detected, PCR and phylogenetic analysis targeting the Anaplasma 16S rRNA gene revealed that the horse was infected with Anaplasma bovis. Although PCR targeting the groEL and gltA genes of A. bovis was not successful, the restriction enzyme fragment length polymorphism assay for differential diagnosis and determination of coinfectivity between Anaplasma phagocytophilum and A. bovis confirmed the pathogen as A. bovis. To the best of our knowledge, this is the first clinical report of A. bovis infection in a horse, suggesting a new reservoir host.

ANALISIS LAMA WAKTU PELAYANAN LABORATORIUM DI RUMAH SAKIT UMUM DAERAH PASAMAN BARAT

Hospital laboratory services is one of the activities in hospitals that support quality health services. One indicator of the success of health services in the field of clinical pathology laboratory services is the waiting time for laboratory services. The standard set for laboratory service outcome waiting time is ≤ 140 minutes for blood chemistry and routine blood. This research analyzed the service time of outpatient laboratory that conducted hematology and clinical chemistry examination in the laboratory of Pasaman Barat Hospital. This research is a type of descriptive analytic research that is quantitative and supported by qualitative using cross sectional approach. The result of the research showed that laboratory service time at RSUD Pasaman Barat fulfilled the standard (≤ 140 minutes) for hematology examination 33.94 minutes, clinical chemistry 83.92 minutes, hematology and clinical chemistry 98 minutes. Based on the results of this study, the stages that contribute to the length of time laboratory services for hematological examination lies in the pre analytical stage, for clinical chemistry examination is located at the analytical stage, as well as for hematology and clinical chemistry examination lies in the analytic stage as well as the factors that affect the length of time laboratory services are human resources that is in the ability of officers and infrastructure facilities

From the Cover: Metabolism Modulation in Different Organs by Silver Nanoparticles: An NMR Metabolomics Study of a Mouse Model.

Although silver nanoparticles (AgNPs) are widely disseminated and show great potential in the biomedical field, there is a recognized need to better understand their action at the metabolic and functional levels. In this work, we have used NMR metabolomics, together with conventional clinical chemistry and histological examination, to characterize multi-organ and systemic metabolic responses to AgNPs intravenously administered to mice at 8 mg/kg body weight (a dose not eliciting overt toxicity). The major target organs of AgNPs accumulation, liver and spleen, showed the greatest metabolic changes, in a clear 2-stage response. In particular, the liver of dosed mice was found to switch from glycogenolysis and lipid storage, at 6 h postinjection, to glycogenesis and lipolysis, at subsequent times up to 48 h. Moreover, metabolites related to antioxidative defense, immunoregulation and detoxification seemed to play a crucial role in avoiding major hepatic damage. The spleen showed several early changes, including depletion of several amino acids, possibly reflecting impairment of hemoglobin recycling, while only a few differences remained at 48 h postinjection. In the heart, the metabolic shift towards TCA cycle intensification and increased ATP production possibly reflected a beneficial adaptation to the presence of AgNPs. On the other hand, the TCA cycle appeared to be down regulated in the lungs of injected mice, which showed signs of inflammation. Thekidneys showed the mildest metabolic response to AgNPs. Overall, this study has shown that NMR metabolomics is a powerful tool to monitor invivo metabolic responses to nanoparticles, revealing unforeseen effects.

Safety evaluation of water-soluble palm fruit bioactives

Water-soluble palm fruit bioactives, derived from the aqueous stream of palm oil processing, have shown anti-diabetogenic effects in rodent models. To assess the safety of potential incorporation of this polyphenol-containing material in food, in vitro bacterial reverse mutation and in vitro chromosome aberration assays were conducted along with a 90-day subchronic toxicity study in Sprague-Dawley rats. Water-soluble palm fruit bioactives were inactive in the Ames and in vitro chromosome aberration assays up to the limit doses of 5000 μg/plate and 5000 μg/mL, respectively. In the 90-day feeding study, water-soluble palm fruit bioactives were administered via gavage at doses 0, 500, 1000 or 2000 mg/kg body weight/day. No significant effects were noted on body weight, food consumption, hematology, clinical chemistry, organ weights, and histopathological examination. The No Observable Adverse Effect Level was considered to be 2000 mg/kg body weight/day, the highest dose tested. These data provide evidence to support the safe use of water-soluble palm fruit bioactives in food or food ingredients.

Lipid-soluble green tea extract: Genotoxicity and subchronic toxicity studies

To assess the potential safety of lipid soluble green tea extract, also referred to as lipid soluble tea polyphenols (LSTP), a series of genotoxicity tests were conducted, including an Ames, in vivo mouse micronucleus, and in vivo mouse sperm abnormality test. The toxicity of LSTP was evaluated in 90- and 30-day feeding studies. LSTP did not show mutagenic activity in the Ames test and no genotoxic potential in the in vivo assays at doses up to 10 g/kg body weight (bw). In the 90-day feeding study, LSTP was given in the diet at levels providing 0, 0.125, 0.25, or 0.50 g/kg bw/day. No significant effects were noted on body weight, food consumption, hematology, clinical chemistry, organ weights, and histopathological examination. The no-observed-adverse-effect level (NOAEL) was therefore considered to be 0.50 g/kg bw/day, the highest dose tested. Likewise, dosing of SD rats by gavage for 30 days also showed no adverse effects of growth, hematology, clinical chemistry, organ weights, or histopathology at doses of 0.58, 1.17, and 2.33 g/kg bw/day. The NOAEL in the 30-day study was considered to be the highest dose tested. These data provide evidence to support the safe use of LSTP in food.

UJI KUALITAS SERUM SIMPANAN TERHADAP KADAR KOLESTEROL DALAM DARAH DI POLTEKKES KEMENKES KALTIM

Clinical Chemistry Examination Guidelines stated several factors may affecting the stability of the specimen i.e. contaminant germs and chemicals, exposure to sunlight, the effects of temperature and metabolism of living cells such as blood cells. Blood specimens should be stored in the form of serum in a refrigerator at a temperature of 2-80 C. This study aimed to compare cholesterol levels of serum with no erythrocyte and with erythrocytes during storage for 3 and 9 days at 2-8ºC. This is an analytical survey to compare cholesterol levels in serum blood during storage. Data was analyzed using Independent Sample t-test. The result showed value p (0.410) is greater than α (0.05), so there is no correlation between serum with erythrocytes and with no erythrocytes in cholesterol at a temperature of 2-8 0C stored for 3 days and the p-value (0.162) is greater than α (0.05) then pat concluded that there was no influence of serum with erythrocytes and without erythrocytes to changes in cholesterol at a temperature of 2-8 0C during storage of 9 days

Acute and subacute toxicity studies of CMICE-013, a novel iodinated rotenone-based myocardial perfusion tracer, in Sprague Dawley rats and Gottingen minipigs

PurposeExtensive acute and subacute toxicities studies are required to evaluate the toxicological profile of the novel cardiac perfusion imaging tracer 123I-CMICE-013 to support applications for clinical trials. MethodsSprague-Dawley rats and Gottingen minipigs received injections of non-radioactive 127I-CMICE-013 at two dosage levels of 1 and 5 μg/kg, and vehicle buffer as control. In the acute toxicity studies, each animal was injected on two occasions 24 h apart and then underwent a 14-day recovery period; in the subacute study, animals received daily injections for 14 days continuously. The health status and mortality of test animals were monitored daily and body weight, food consumption, physiological and biochemical parameters were measured at various time points during the study. Animals were euthanized at the end of the studies and dissected for pathologic examination of organs and tissues. ResultsThe acute and subacute administrations of injections of the non-radioactive CMICE-013 in rats and minipigs were well tolerated. Little to no dosing-related adverse effects were observed in animal body and organ weights, hematology, coagulation, clinical chemistry, urinalysis, ophthalmoscopy, electrocardiograms, heart rates, blood pressure, macroscopic and microscopic examination of the preserved animal tissues including the brain. ConclusionThe lack of adverse effects from acute and subacute dosing suggest that the CMICE-013 injection solution has a reasonable safety margin within the designed concentration range to be utilized in imaging applications. The dosage level of 5 μg/kg was considered the no adverse effect level for both rats and minipigs based on our acute and subacute studies.

ASSESSING EFFECTS OF EQUISETUM RAMOSISSIMUM EXTRACT ON HEMATOLOGICAL AND SERUM BIOCHEMICAL PARAMETERS IN PREGNANT SPRAGUE-DAWLEY RATS

Background: As a medicinal herb, Equisetum ramossisemum has been utilized for centuries as a diuretic and has been&#x0D; recommended for different disorders. The aim of this study was to investigate the maternal toxicity of aerial parts of Equisetum&#x0D; ramosissimum extract on pregnant Sprague-Dawley rats.&#x0D; Methods: Females were mated and the coupling time was recorded at gestation day 0– E0. Four experimental groups I, II, III, and&#x0D; IV, received daily gavage doses of 0 mg, 500 mg, 250 mg, and 125 mg/kg, respectively, of Equisetum ramosissimum extract.&#x0D; Pregnant rats were observed for mortality and toxicological effects during daily treatment. On day E20, samples of blood were&#x0D; withdrawn from the retro-orbital sinus under light ether anaesthesia for haematological and clinical chemistry examinations.&#x0D; Results: Data analyses detected significant differences in biochemical and haematological parameters between the control group and&#x0D; other groups receiving extract.&#x0D; Conclusion: This study constitutes a first approach to defining adverse effects of using Equisetum ramosissimum as a medicinal&#x0D; plant during pregnancy. Daily gavage doses of Equisetum ramosissimum extract produced significant differences in biochemical and&#x0D; haematological parameters in pregnant Sprague-Dawley rats as compared to the control group.

A 90-day subchronic toxicity study with sodium formononetin-3′-sulphonate (Sul-F) delivered to dogs via intravenous administration

Sodium formononetin-3′-sulphonate (Sul-F) is a water-soluble derivate of formononetin, and an increasing number of studies have shown that Sul-F not only possesses favorable water solubility but also exhibits good lipid-lowering and bioactivities. In the current study, the toxicity of Sul-F was evaluated in dogs after 90-day intravenous infusion. Dogs were treated with Sul-F at dose of 0, 33.3, 100, and 300 mg/kg, and observed for 90-day followed by 28-day recovery period. Weekly measurement of body weight, temperature and food consumption were conducted. Ophthalmoscopy, ECG examination, urinalysis, serum biochemistry and hematology examination were performed at pre-test, on days 45 and 90, and following by 28-day recovery period. Histological examination was performed on day 90 and 28-day recovery period. No mortality, ophthalmic abnormalities or treatment-related findings in body weight, clinical chemistry, hematology, and histopathological examination were detected. However, a white crystal (non-metabolic Sul-F), transient vomiting and recoverable vascular stimulation were observed in 300 mg/kg/day Sul-F treated dogs. Under the conditions, the no-observed-adverse-effect-level (NOAEL) for Sul-F was 100 mg/kg in dogs.