scholarly journals Detection of hepatocarcinogens by combination of liver micronucleus assay and histopathological examination in 2-week or 4-week repeated dose studies

2022 ◽  
Vol 44 (1) ◽  
Author(s):  
Shuichi Hamada ◽  
Miyuki Shigano ◽  
Yumi Wako ◽  
Kazufumi Kawasako ◽  
Kensuke Satomoto ◽  
...  

Abstract Background Currently, revisions to the ICH S1 guidance on rodent carcinogenicity testing are being proposed. Application of this approach would reduce the use of animals in accordance with the 3Rs principles (reduce/refine/replace). The method would also shift resources to focus on more scientific mechanism-based carcinogenicity assessments and promote safe and ethical development of new small molecule pharmaceuticals. In the revised draft, findings such as cellular hypertrophy, diffuse and/or focal cellular hyperplasia, persistent tissue injury and/or chronic inflammation, preneoplastic changes, and tumors are listed as histopathology findings of particular interest for identifying carcinogenic potential. In order to predict hepatocarcinogenicity of test chemicals based on the results from 2- or 4-week repeated dose studies, we retrospectively reanalyzed the results of a previous collaborative study on the liver micronucleus assay. We focused on liver micronucleus induction in combination with histopathological changes including hypertrophy, proliferation of oval cells or bile duct epithelial cells, tissue injuries, regenerative changes, and inflammatory changes as the early responses of hepatocarcinogenesis. For these early responses, A total of 20 carcinogens, including 14 genotoxic hepatocarcinogens (Group A) and 6 non-liver-targeted genotoxic carcinogens (Group B) were evaluated. Results In the Group A chemicals, 5 chemicals (NPYR, MDA, NDPA, 2,6-DNT, and NMOR) showed all of the 6 early responses in hepatocarcinogenesis. Five chemicals (DMN, 2,4-DNT, QUN, 2-AAF, and TAA) showed 4 responses, and 4 chemicals (DAB, 2-NP, MCT, and Sudan I) showed 3 responses. All chemicals exhibited at least 3 early responses. Contrarily, in the Group B chemicals (6 chemicals), 3 of the 6 early responses were observed in 1 chemical (MNNG). No more than two responses were observed in 3 chemicals (MMC, MMS, and KA), and no responses were observed in 2 chemicals (CP and KBrO3). Conclusion Evaluation of liver micronucleus induction in combination with histopathological examination is useful for detecting hepatocarcinogens. This assay takes much less time than routine long-term carcinogenicity studies.

Author(s):  
Nutan Punchkande ◽  
Rukmani Dewangan ◽  
Raju Sharda ◽  
D. Jolhe ◽  
Dhaleshwari Sahu ◽  
...  

Background: Canine transmissible venereal tumour (CTVT) also known as infectious sarcoma, venereal granuloma, transmissible lymphosarcoma or sticker tumour is usually transmitted through coitus and mainly affects the external genitalia of young sexually matured dogs. Surgery, chemotherapy, radiotherapy and immunotherapy are considered as effective treatment protocols. Therefore, depending upon the availability present study was designed to investigate the efficacy of different surgico-chemotherapeutic protocols for treatment of canine transmissible venereal tumour.Methods: The study was conducted during January 2018 to July 2018 at the Teaching Veterinary Clinical Complex (TVCC) and Department of Veterinary Surgery and Radiology, College of Veterinary Science and A.H., Anjora, Durg (C.G.) on 18 canines of various breed, irrespective of age, sex and divided into three groups consisting 6 animals in each group. Group A was treated with surgical excision of tumour only where as Group B and Group C were treated with surgical excision of tumour followed by administration of Doxorubicin (30mg/m2) BSA and Vincristine sulphate (0.025 mg/kg) intravenously alongwith DNS at 7th and 14th post-operative days respectively. Different physiological and haemato-biochemical parameters (Hb, PCV, TLC, TPC, DLC, serum glucose, TSP, SUN, SC, ALT, AST and ALP) were recorded preoperatively, postoperatively and after chemotherapy at 10th, 30th and 60th days intervals.Result: The present investigation showed transient changes in physiological and haemato-biochemical parameters before, post surgery and post chemotherapeutic management and was within normal range. Histopathological examination revealed confluent sheet of tumour cells arranged in large round oval or polyhedral shaped distributed in tight clusters or cords. Group A showed mild to moderated reoccurrence while Group B showed minimum reoccurrence. Group C showed no reoccurrence. Thus, surgery combined with vincristine therapy is most effective for treating dogs suffering with transmissible venereal tumour.


2021 ◽  
Vol 8 (4) ◽  
pp. 1195
Author(s):  
P. Ganesh Kumar ◽  
K. Raja ◽  
P. Haritha ◽  
A. D. Saravanakumari ◽  
D. Shanthi ◽  
...  

Background: Diabetes mellitus and its complications are rising. Managing the diabetic foot wound is very challenging. Early intervention and intense management using modern technique will improve the diabetic wounds for a definitive procedure and also prevent, reduce the level of amputation of extremity. Our study compares the microbiological and histopathological results of diabetic wounds managed by conventional dressing and VAC (vacuum assisted closure) therapy.Methods: This was an institutional based prospective study conducted between July 2018 and July 2019 consisting of 50 patients with diabetic wound of lower extremities. Patients were divided into group A- 25 patients underwent conventional dressing and group B- 25 patients underwent negative pressure wound therapy (NPWT). Wound swab and tissue biopsy was obtained on day 0 and day 10 from both groups and compared.Results: Among patients, 76% and 24% were males and females respectively. Histopathologically, necrosis and inflammatory cell infiltrate were significantly decreased in group B compared to group A. Angiogenesis increased notably in group B. On microbiological grounds, from both groups Pseudomonas aeruginosa was found to be the most common organism on day 0 and 10. But the prevalence of infection in group B was grossly reduced when compared to group A.Conclusions: VAC therapy is a better modality to treat diabetic wound compared to conventional dressing as it accelerates the healing of a chronic wound by increasing angiogenesis and decreasing necrosis, inflammatory cell infiltrate and microbial growth.


2020 ◽  
Vol 57 (4) ◽  
Author(s):  
Wafaa Abd El-Ghany ◽  
Hanan Ali Ahmed ◽  
Ali Zaher Qandoos ◽  
Mohamed Abd El-Rahman Bosila Bosila

This study was carried out to evaluate the efficacy of vaccination of layer chickens with inactivated FC bacterin prepared from local Egyptian strains of Pasteurella multocida (P. multocida). A total of 200 layer chickens were divided into 5 equal groups, 40 for each. At the age of 6 weeks, chickens in groups (A) and (B) were vaccinated with P. multocida serotypes A:1 and A:3, respectively, booster doses were given after 3 weeks (9 weeks old) and challenge was done with virulent serotypes A:1 and A:3 at 2 weeks later (11 weeks old). Chickens in groups (C) and (D) were not vaccinated, only challenged with P. multocida serotype A:1 and A:3, respectively. Birds in group (E) were kept as non-vaccinated and non-challenged. Blood samples were collected weekly from all groups for humoral immune response. All the birds were kept under observation for signs, mortalities, lesions and re-isolation of challenging organism and for histopathological examination. Results of the mean Enzyme Linked Immuno-Sorbent Assay (ELISA) revealed that the highest level was at 5 weeks post vaccination as the titers reached to 3970 in group (A) and 3905 in group (B). The clinical signs, mortality rate and lesions were mild in the vaccinated birds while severe lesions were in non-vaccinated and challenged birds. The protection rates were 85 % and 80 % in groups (A) and (B); respectively, while 10 % and 20 % in groups (C) and (D); respectively. The re-isolation rates of P. multocida after challenge were 95 % and 90 % in non-vaccinated-challenged birds with P. multocida serotypes A:1 and A:3; respectively, while they were 25 % and 15 % in vaccinated-challenged groups with P. multocida serotypes A:1 and A:3; respectively. Histopathological examination of P. multocida vaccinated-challenged birds revealed mild to no microscopic lesions when compared with non-vaccinated challenged chickens. In conclusion, the prepared FC inactivated bacterin from the local Egyptian predominant P. multocida serovars proved efficacy and protection of layer chickens. Key words: Pasteurella multocida; chickens; immunization; protection; Egypt UČINKOVITOST CEPLJENJA KOKOŠI NESNIC Z INAKTIVIRANO BAKTERIJO KOLERE PERJADI, PRIPRAVLJENE IZ LOKALNIH EGIPTOVSKIH SEVOV BAKTERIJE Pasteurella multocida Povzetek: Raziskava je bila izvedena z namenom ocenitve učinkovitosti cepljenja kokoši nesnic z inaktivirano bakterijo FC, pripravljeno iz lokalnih egiptovskih sevov bakterije Pasteurella multocida (P. multocida). Skupno 200 kokoši nesnic je bilo razdeljenih v 5 enakih skupin. V vsaki skupini je bilo 40 kokoši. Pri 6 tednih smo kokoši v skupinah A in B cepili s serotipoma P. multocida A:1 in A:3, po 3 tednih, ko so bile živali stare 9 tednov, so dobile poživitvene doze cepiva. Po dveh tednih (v starosti 11 tednov) so bile kokoši okužene z virulentnima serotipoma A:1 in A:3. Piščanci v skupinah C in D niso bili cepljeni temveč samo okuženi s serotipoma A:1 in A:3. Kokoši v skupini E niso bile niti cepljene, niti okužene. Vzorci krvi so bili odvzeti pri vseh skupinah tedensko za preverjanje humoralnega imunskega odziva. Vse kokoši smo stalno opazovali in beležili prisotnost bolezenskih znakov, različnih ran in umiranje kokoši. Pri poginulih kokoših smo osamili bakterije ter opravili histopatološki pregled. Rezultati encimsko-imunskega testa (ELISA) so pokazali da je bila najvišja stopnja zaščite dosežena 5 tednov po cepljenju, saj so titri dosegli 3970 v skupini A in 3905 v skupini B. Klinični znaki, stopnja umrljivosti in rane so bili pri cepljenih kokoših blagi, hude rane pa so bile vidne pri necepljenih in okuženih kokoših. Stopnja zaščite je bila v skupinah A in B 85- oziroma 80-odstotna, v skupinah C in D pa 10- oziroma 20-odstotna. Stopnje ponovne izolacije P. multocida po okužbi so bile 90 in 95 odstotkov pri kokoših, ki niso bile cepljene, medtem, ko so bile v skupinah, ki so bile okužene s P. multocida serotipa A:1 in A:3 15- in 25-odstotkov. Histopatološki pregled cepljenih in okuženih kokoši je pokazal popolno odsotnost ali prisotnost blagih mikroskopskih poškodb, medtem ko so imele necepljene okužene kokoši bolj obsežne histopatološke poškodbe. Pripravljena inaktivirana bakterija FC iz lokalnih egiptovskih prevladujočih serovarov P. multocide se je izkazala za učinkovito zaščito kokoši nesnic.Ključne besede: Pasteurella multocida; kokoši; imunizacija; zaščita; Egipt


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Ashwin Rammohan ◽  
Sathya D. Cherukuri ◽  
Jeswanth Sathyanesan ◽  
Ravichandran Palaniappan ◽  
Manoharan Govindan

Background. Xanthogranulomatous cholecystitis (XGC) is often misdiagnosed as gallbladder cancer (GBC). We aimed to determine the preoperative characteristics that could potentially aid in an accurate diagnosis of XGC masquerading as GBC.Methods. An analysis of patients operated upon with a preoperative diagnosis of GBC between January 2008 and December 2012 was conducted to determine the clinical and radiological features which could assist in a preoperative diagnosis of XGC.Results. Out of 77 patients who underwent radical cholecystectomy, 16 were reported as XGC on final histopathology (Group A), while 60 were GBC (Group B). The incidences of abdominal pain, cholelithiasis, choledocholithiasis, and acute cholecystitis were significantly higher in Group A, while anorexia and weight loss were higher in Group B. On CT, diffuse gallbladder wall thickening, continuous mucosal line enhancement, and submucosal hypoattenuated nodules were significant findings in Group A. CT findings on retrospect revealed at least one of these findings in 68.7% of the cases.Conclusion. Differentiating XGC from GBC is difficult, and a definitive diagnosis still necessitates a histopathological examination. An accurate preoperative diagnosis requires an integrated review of clinical and characteristic radiological features, the presence of which may help avoid radical resection and avoidable morbidity in selected cases.


2008 ◽  
Vol 23 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Carlos Henrique Marques dos Santos ◽  
Otoni Moreira Gomes ◽  
José Carlos Dorsa Vieira Pontes ◽  
Luciana Nakao Odashiro Miiji ◽  
Marco Aurélio Feltrin Bispo

PURPOSE: To evaluate the effect of the ischemic preconditioning and the ischemic postconditioning over the tissue injury in the intestinal mucosa of rats undergoing the procedure of mesenteric ischemia and reperfusion. METHODS: Thirty Wistar rats were studied, divided in three groups: group A, undergoing mesenteric ischemia (30 minutes) and reperfusion (60 minutes); group B, mesenteric ischemia and reperfusion preceded by ischemic preconditioning; group C, mesenteric ischemia and reperfusion and, before the beginning of reperfusion, the ischemic postconditioning was performed. At the end, a segment of the small intestine was dissected for histological analysis. The results were evaluated using the CHIU et al.6 classification followed by the statistic treatment. RESULTS: The mean values of the tissue injury levels were: group A, 3.5; group B, 1.2; and group C, 1. The difference between the result of group A with the results of groups B and C was considered statistically significant (p < 0,05). CONCLUSION: The ischemic preconditioning and postconditioning are able to minimize the tissue injury in the intestines of rats that underwent the procedure of mesenteric ischemia and reperfusion.


Author(s):  
Dr. S. E. Gowtham

Abstract: The point of the executives is to ease the pain rapidly and improve practical capacity. NSAIDs are the primary line treatment. Serratiopeptidase is the proteolytic enzyme. The challenge lies in deciding whether only NSAIDs or NSAIDs with proteolytic enzyme will give more prominent indicative help, while additionally being savvy. the primary goal is to think about the adequacy of diclofenac with paracetamol and diclofenac with serratiopeptidase in the administration of delicate tisssue injury. This prospective, open label, observational study was conducted at a tertiary care hospital. Patients over 18 years of age and presenting with soft tissue injury pain (elbow pain, knee pain, general pain, back pain ) of less than 6 weeks duration were enrolled in the study. Forty patients with soft tissue injury pain were randomized into two groups: Group A got diclofenac with paracetamol (50mg/325mg) double a day and Group B got diclofenac with serratiopeptidase (50mg/10mg) double a day for 1 week. The Numerical Rating Scale (NRS) determined the clinically significant results. The decrease in pain intensity in Group B was (MEAN= 3.76), while in Group A it was (MEAN= 3.93). The average cost-effectiveness ratio indicated that diclofenac wit paracetamol was the dominant treatment over diclofenac with serratiopeptidase. Therefore, diclofenacc with paracetamol was found to be the cost-effective option for soft tissue injury pain relief in for 1 week. Both diclofenac wit paracetamol and diclofenac with serratiopeptidase. were clinically effective in reducing the pain intensity and in improving functional ability. H owever, diclofenac wit paracetamol was found to be the cost-effective intervention. Keywords: Paracetamol, diclofenac, Serratiopeptidase, soft tissue injury, pain.


2021 ◽  
Vol 6 (4) ◽  
pp. 635-640
Author(s):  
Emdadul Hoque ◽  
Khaled Mahmud Sujan ◽  
Md Suman Mia ◽  
Md Iqramul Haque ◽  
Afrina Mustari ◽  
...  

Bisphenol-A (BPA) is one of the highest volume chemicals produced world-wide and used in the manufacture of plastics and epoxy resins that are pervasive in our environment and daily lives. The present research was carried out to investigate the effects of two different doses of Bisphenol-A (BPA) on the body weight, hematological parameters and patho-physiological changes of kidney in mice. For this study, fifteen mice, 6 to 8 weeks of age with an average bwt 27.10±0.5 gm, were randomly divided into three groups (n= 5). Group A (control) received only normal mouse pellet while group B and group C received pellet mixed with BPA @ 50 mg and 100 mg / kg bwt daily for 12 weeks, respectively. At the end of the experiment, blood and tissues were collected and processed for hematological and histopathological examination. Results showed that BPA- treated mice caused significant elevation (p<0.01) in weight gain even treated with low dose (50mg) of BPA. The mice exposed to high dose of BPA (100 mg) showed marked reduction (p<0.05) in total erythrocyte count (TEC), significant decreased (p<0.01) in hemoglobin concentration (Hb) and packed cell volume (PCV). Histopathological alterations were detected in the kidneys of BPA-treated mice. In conclusion, this study suggested that BPA exerts deleterious impacts on hematological parameters including association with renal injuries. Asian J. Med. Biol. Res. December 2020, 6(4): 635-640


2010 ◽  
Vol 4 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Maria Shabbir Saria ◽  
Masoom Raza Mirza ◽  
Lubna Habib ◽  
Muhammad Zubair

The aim of this study was to determine the significance of various reproductive risk factors amongstPakistani women suffering from breast carcinoma. This observational study was carried out fromMarch 2007 to February 2009 at three hospitals. The women who presented with breast swellingwith or without discharge from nipple were included in the study. The diagnosis of breast cancer wasconfirmed by histopathological examination. A questionnaire included history and various reproductiverisk factors. The study patients were divided into two groups by their menopausal history – premenopausaland post-menopausal as ‘group A’ and ‘group B’, respectively. A total of 70 patients hadthe diagnosis of breast cancer. Of them, 32 were in group A and 38 in group B. Regarding agedistribution, 49% were found in ≥51 years of age and 29% in the age group 30 – 40 years. The meanage at menarche was 13.3 years in group A and 12.4 years in group B. Nulliparity was seen in12.5% cases in group A and 5.26% in group B. History of first full term pregnancy (FFTP) belowthe age of 20 was present in majority of cases in both groups though higher in group B. Breast cancerin post-menopausal women was exclusively found among those who had early menarche (<=11years) and was more frequent among those who had FFTP below 20 years of age compared with thepre-menopausal group (88% vs. 66%). The study showed higher frequency of breast cancer in postmenopausalwomen having early menarche and also more frequent among those with early FFTP.Parity, breast feeding, oral contraceptive pill use were not related to breast cancer.Ibrahim Med. Coll. J. 2010; 4(1): 1-3Indexing Words: Breast carcinoma; risk factors; genetics.DOI: 10.3329/imcj.v4i1.5926


Sign in / Sign up

Export Citation Format

Share Document