Strengthening retina eye care services in Nepal: retina eye care of Nepal project.

BACKGROUND: Retinal diseases are very difficult to treat. So, early diagnoses and preventions are very important. But, few eye doctors can treat patients with retinal diseases in Nepal. Retina Eye Care of Nepal (RECON) project was designed to strengthen retina eye care services in Nepal. METHODS: RECON was implemented from May 2016 to February 2019 in Nepal. Four Master Eye Doctors (MED) received Training of Trainers (TOT) from Tokushima University, Japan. MEDs developed training materials for different cadres of ophthalmic human resources, enhanced retina eye care facilities, and conducted retina-screening camp in Nepal. RESULTS: Twenty ophthalmologists, 16 optometrists, 48 ophthalmic assistants and 17 ophthalmic nurses, 76 physicians and 28 health workers were trained in retina care. Eight outreach retina camps were conducted. CONCLUSIONS: The project was a novel approach to strengthen retina services in Nepal. The aim of the project was accomplished with the ultimate benefits to the needy retina patients who otherwise were going to miss the retina services.

A Unique Experience of Retinal Diseases Screening in Nepal.

BACKGROUND: Recently, the number of retinal patients is increasing in Nepal. The retinal problems are the second common cause of blindness in Nepal. Retinal diseases are challenging to manage due to the lack of simple and cost-effective screening methods, limited human resources, poverty, and lack of awareness in Nepal. Hospital for Children, Eye, ENT & Rehabilitation Services (CHEERS), Nepal conducted retina screening camps and education in communities through Retina Eye Care of Nepal project (RECON) in the years 2017 and 2018. MATERIALS AND METHODS: We screened retinal patients with an indirect ophthalmoscope coupled with plus 20 Dioptre lens and portable fundus camera. We referred the patients needing interventions to the base hospital (CHEERS) using a screening algorithm, where they received retinal laser and surgery. Besides, we also provided on-site educational programs for retinal disease awareness to the community. RESULTS: Retinal problems found from two static outreach clinics (SORC) and a day screening and treatment service (DSTS) were 18.3%, 20%, and 20%, respectively, while from a remote rural health camp (RRHC) was 2.61%. Likewise, patients referred to CHEERS for retinal laser or other retinal interventions were 15%, 16.6%, 16%, and 1.96% from 2 SORCs, 1 DSTS, and 1 RRHC, respectively. CONCLUSION: Retina camp is a cost-effective approach to early detection and referral for retinal-related vision impairment patients. It is also one opportunity to educate the community. The purpose of the project was to provide retina care to the community who otherwise could not afford it. We recommend a similar screening model on a large scale in a low-resource setting for the maximum benefits to the rural community.

Neoadjuvant chemotherapy plus surgery for high-risk advanced gastric cancer: long-term results of KDOG1001 trial.

PURPOSE: The purpose of this study is to evaluate the long-term survival outcomes of KDOG1001 trial after a minimum follow-up of 3 years. METHODS: Patients with bulky N2 lymph nodes, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) received up to four 28-day cycles of DCS neoadjuvant chemotherapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 lymphadenectomy plus adjuvant S-1 therapy for 1 year. The final preplanned analysis of long-term outcomes including overall survival and relapse-free survival was conducted after minimum follow-up of 3 years. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN 000003642, and has been completed. RESULTS: From May 2010 through January 2017, 40 patients were enrolled. All included patients underwent neoadjuvant chemotherapy with DCS followed by gastrectomy with D2 lymphadenectomy, and 32 (80%) completed adjuvant S-1 therapy for 1 year. After a median follow-up for surviving patients of 68 months at the last follow-up in January 2020, 3-year overall survival rate was 77.5% (95% confidence interval 62.1-87.9%), while 3-year relapse-free survival rate was 62.5% (95% confidence interval 46.8-76.0%). CONCLUSION: Neoadjuvant chemotherapy with 4 cycles of DCS followed by D2 gastrectomy plus adjuvant S-1 was associated with relatively good long-term oncologic outcomes for patients with the high-risk gastric cancer.

An Integrated Genomic and Transcriptomic Analysis Reveals Candidates of Susceptibility Genes for Crohn's Disease in Japanese Populations.

Expression quantitative trait locus (eQTL) analyses have enabled us to predict the function of disease susceptibility SNPs. However, eQTL for the effector memory T cells (TEM) located in the lamina propria mononuclear cells (LPMCs), which play an important role in Crohn's disease (CD), are not yet available. Thus, we conducted RNA sequencing and eQTL analyses of TEM cells located in the LPMCs from IBD patients (n = 20). Genome-wide association study (GWAS) was performed using genotyping data of 713 Japanese CD patients and 2,063 controls. We compared the results of GWAS and eQTL of TEM, and also performed a transcriptome-wide association study using eQTL from Genotype Tissue Expression project. By eQTL analyses of TEM, correlations of possible candidates were confirmed in 22,632 pairs and 2,463 genes. Among these candidates, 19 SNPs which showed significant correlation with tenascin-XA (TNXA) expression were significantly associated with CD in GWAS. By TWAS, TNFSF15 (FDR = 1.35e-13) in whole blood, ERV3-1 (FDR = 2.18e-2) in lymphocytes, and ZNF713 (FDR = 3.04e-2) in the sigmoid colon was significantly associated with CD. By conducting integration analyses using GWAS and eQTL data, we confirmed multiple gene transcripts are involved in the development of CD.

[Conversion Surgery for Locally Advanced Unresectable Pancreatic Cancer Treated with FOLFIRINOX Therapy and Proton Beam Therapy Combined with S-1 Chemotherapy-A Case Report].

We report a case of locally advanced unresectable(UR-LA)pancreatic cancer in a patient who underwent conversion surgery after FOLFIRINOX and proton beam therapy(PBT)combined with S-1. A 68-year-old woman was referred to our hospital for a pancreatic tumor. The abdominal CT scan revealed a 40mm pancreatic body tumor with an abutment(>180°) of the celiac artery and the superior mesenteric artery. Moreover, the tumor was classified as UR-LA with a contact to the abdominal aorta. The tumor was histologically diagnosed as adenocarcinoma via an endoscopic ultrasound-guided fine-nee- dle aspiration. After 2 courses of FOLFIRINOX, PBT(50 GyE/25 Fr)combined with S-1 were administered. The tumor shrunk to 30mm at the CT scan. After 5 courses of FOLFIRINOX, the tumor reduced to 20 mm. No distant metastasis or malignant cells in abdominal washing cytology was detected using staging laparoscopy. Then, distal pancreatectomy with celiac axis resection(DP-CAR)was performed. According to the General Rules for the Study of Pancreatic Cancer(7th edition)from Japan Pancreas Society, the histological findings were suggestive of ypT3, ypN0, R0, and Grade 3 histological effect. The patient had a Grade A delayed gastric emptying post-operation. He was discharged 35 days after the surgery and has been alive without recurrence on imaging for 11 months post-operation.

Air Bubble Technique for Fundus Visualization during Vitrectomy in Aphakia.

PURPOSE: To evaluate the efficacy and safety of air bubble technique for vitrectomy in aphakia. STUDY DESIGN: Prospective interventional uncontrolled case series. METHODS: This study included 53 eyes of 53 patients who are phakic and indicated for phacovitrectomy (7 eyes, group 1), aphakic and indicated for vitrectomy (22 eyes, group 2), or underwent unplanned vitrectomy for immediate management of a phacoemulsification surgery complicated by rupture posterior capsule with dropped nucleus, fragments, or IOL (24 eyes, group 3). Cases with complicated vitreoretinal pathology were not included in this study. All vitrectomy surgeries were conducted by the air bubble technique in the anterior chamber. Main outcomes included anatomical success, visual acuity, and intraoperative and postoperative complications. RESULTS: The surgical success was achieved in 50 eyes (94.3%). Conversion to BIOM viewing system was needed in the retinal detachment cases of groups 1 and 2. The mean overall LogMAR visual acuity was significantly improved from 1.29 ± 0.58 preoperatively to 0.56 ± 0.19 at the final visit, 6 months postoperatively (P < 0.001). CONCLUSION: The air bubble technique as visualization method for vitrectomy in aphakia is an effective and cheap technique for immediate management of complications of phacoemulsification surgery. This trial is registered with Pan African Clinical Trial Registry PACTR201709002466296.

Secondary neuroendocrine tumor after allogeneic bone marrow transplantation.

Here we report a case of aggressive neuroendocrine tumor (NET), which is an extremely rare secondary solid tumor that occurs after allogeneic hematopoietic cell transplantation (allo-HSCT). A patient with chronic active Epstein-Barr virus infection received allo-HSCT from an HLA-DR two allele-mismatched unrelated donor. Four years later, he developed NET with multiple metastases. He received thoraco-abdominal irradiation as a conditioning regimen, and developed repeated episodes of intestinal graft-versus-host disease, for which he received long-term immunosuppressive therapy. Although these factors may be potential contributing factors to the development of secondary NET, the exact pathogenesis remains unclear.

Expression of intraocular peroxisome proliferator-activated receptor gamma in patients with proliferative diabetic retinopathy.

AIMS: To determine whether peroxisome proliferator-activated receptor gamma (PPARγ), which is recognized as a component of the exosomes circulating in plasma, is expressed intraocularly in patients with proliferative diabetic retinopathy (PDR). METHODS: The concentrations of PPARγ and vascular endothelial growth factor (VEGF) in the aqueous humor and vitreous of 50 eyes with PDR and 38 control eyes were determined by ELISA. The levels of the mRNA and protein of PPARγ were determined in proliferative membranes from 12 PDR and 5 control eyes by quantitative RT-PCR and immunohistochemical analyses. RESULTS: PPARγ was detected in the culture media of human umbilical vein endothelial cells indicating that PPARγ can be released into the extracellular fluid. The PPARγ concentrations in the aqueous humor and vitreous fluid were significantly higher in PDR patients than in controls (P<0.0005). There was a significant positive correlation between the PPARγ and VEGF concentrations (P<0.0005). The level of PPARγ increased as the clinical stage advanced. The expressions of the mRNA and protein of PPARγ were higher in the membranes of PDR than those of controls. Anti-VEGF therapy significantly reduced the VEGF concentration (P<0.0001) but not the PPARγ concentration. CONCLUSIONS: PPARγ may play an important role in the pathogenesis of PDR.

Achromobacter buckle infection diagnosed by a 16S rDNA clone library analysis: a case report.

BACKGROUND: In clinical settings, bacterial infections are usually diagnosed by isolation of colonies after laboratory cultivation followed by species identification with biochemical tests. However, biochemical tests result in misidentification due to similar phenotypes of closely related species. In such cases, 16S rDNA sequence analysis is useful. Herein, we report the first case of an Achromobacter-associated buckle infection that was diagnosed by 16S rDNA sequence analysis. This report highlights the significance of Achromobacter spp. in device-related ophthalmic infections. CASE PRESENTATION: A 56-year-old woman, who had received buckling surgery using a silicone solid tire for retinal detachment eighteen years prior to this study, presented purulent eye discharge and conjunctival hyperemia in her right eye. Buckle infection was suspected and the buckle material was removed. Isolates from cultures of preoperative discharge and from deposits on the operatively removed buckle material were initially identified as Alcaligenes and Corynebacterium species. However, sequence analysis of a 16S rDNA clone library using the DNA extracted from the deposits on the buckle material demonstrated that all of the 16S rDNA sequences most closely matched those of Achromobacter spp. We concluded that the initial misdiagnosis of this case as an Alcaligenes buckle infection was due to the unreliability of the biochemical test in discriminating Achromobacter and Alcaligenes species due to their close taxonomic positions and similar phenotypes. Corynebacterium species were found to be contaminants from the ocular surface. CONCLUSIONS: Achromobacter spp. should be recognized as causative agents for device-related ophthalmic infections. Molecular species identification by 16S rDNA sequence analysis should be combined with conventional cultivation techniques to investigate the significance of Achromobacter spp. in ophthalmic infections.

Spectral-domain optical coherence tomographic and fundus autofluorescence findings in eyes with primary intraocular lymphoma.

BACKGROUND: The purpose of this study was to evaluate the findings on spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) in three eyes with primary intraocular lymphoma (PIOL). METHODS: The medical records of three eyes from three patients with biopsy-proven PIOL and retinal infiltrations were reviewed. The SD-OCT and fluorescein angiographic findings were evaluated in the three eyes and FAF images in two eyes. RESULTS: The PIOL in the three patients was monocular. Vitreous opacities and retinal infiltrations were observed in the three eyes, and iritis was present in two eyes. The cytologic diagnosis was class V in two eyes and class III in one eye. The interleukin-10/interleukin-6 ratio was >1.0 in the vitreous and aqueous humor of the three eyes. The FAF images for two eyes showed abnormal granular hyperautofluorescence and hypoautofluorescence which were the reverse of the pattern in the fluorescein angiographic images. In all three eyes, SD-OCT showed hyper-reflective infiltrations at the level of the retinal pigment epithelium (RPE), a separation of the Bruch membrane from the RPE, damage to the RPE, disruption of the photoreceptor inner segment/outer segment junction, and multiple hyper-reflective signals in the inner retina. CONCLUSION: Because of the characteristic FAF and SD-OCT findings in these eyes with PIOL, we suggest that these noninvasive methods may be used for a rapid diagnosis of PIOL and also for understanding the pathology of PIOL.

Changes of fundus autofluorescence and spectral-domain optical coherence tomographic findings after treatment of primary intraocular lymphoma.

BACKGROUND: We report the fundus autofluorescence (FAF), spectral-domain optical coherence tomographic (SD-OCT), microperimetric, and multifocal electroretinographic (mfERG) findings before, during, and after successful treatment of a primary intraocular lymphoma (PIOL). FINDINGS: A 57-year-old man had biopsy-proven PIOL in his left eye, and he was treated with intravitreal methotrexate injections for 8 months. Before treatment, fundus examination disclosed many small, yellow lesions with distinct boundaries in the posterior fundus which became atrophic 9 months after the initial treatment. FAF showed a pattern of granular hypoautofluorescence and hyperautofluorescence before the treatments and patchy hypoautofluorescence corresponding to retinal pigment epithelial (RPE) atrophy after the treatments. SD-OCT showed increased nodularity at the level of and above the RPE, a separation of Bruch membrane from the RPE, partial damage of the RPE, disruption of the photoreceptor inner segment/outer segment (IS/OS) junction, multiple hyperreflective signals in the inner retina, foveal thinning, and parafoveal thickening. After treatment, the hyperreflective infiltrations in the inner retina were markedly decreased, and the RPE and IS/OS junction were restored. The foveal thinning and parafoveal thickening resolved, and the central choroidal thickness decreased. During the follow-up, the mfERGs remained decreased. In contrast, microperimetry showed a partial improvement of the retinal sensitivity. CONCLUSION: FAF and SD-OCT are useful noninvasive methods to evaluate the retinal and choroidal changes before and after treatment of PIOL. Our results suggest that visual recovery after successful treatment may be limited once macula is infiltrated.

[A case of advanced gallbladder cancer with mediastinum lymph node metastasis successfully treated with multimodality therapy].

A 69 -year-old female with advanced gallbladder cancer underwent cholecystectomy, S4a/S5 segmentectomy of the liver, and resection of the extra-hepatic bile duct in October 2005. Adjuvant chemotherapy consisted of gemcitabine (GEM) and tegafururacil (UFT) administered consecutively. Four years after surgery, computed tomography revealed a single enlarged lymph node in the mediastinum, along with ¹8F-fluorodeoxyglucose accumulation and increased carcinoembryonic antigen (CEA) levels. Therefore, the mediastinal lymph node was considered to be a metastasis and GEM was readministered. Although the patient was treated with GEM for 1 year, the accumulation of 18F-fluorodeoxyglucose in the lymph node remained elevated. No other distant metastases were detected. Abronchoscopic biopsy histologically confirmed mucinous adenocarcinoma in the lymph node. Thus, the mediastinal lymph node was resected. Post-surgery, there was no evidence of recurrence during the 30-month follow up period without chemotherapy. Herein, we report a successful case of surgical treatment for solitary mediastinal lymph node metastasis of gallbladder cancer and review the relevant literature.

[A case report of complete pathological response of a locally advanced rectal cancer after long term chemotherapy].

A-39-year-old man presented to a nearby clinic owing to long-term diarrhea and painful defecation. He was diagnosed with a well-differentiated tubular adenocarcinoma of the rectosigmoid and underwent a laparotomy at another hospital. At surgery, the tumor was seen to deeply invade into the urinary bladder with the presence of intra-abdominal abscess. Loop sigmoid colostomy was performed due to possible invasion into the pelvic wall and peritoneal dissemination. The patient was referred to the our hospital for systemic chemotherapy. After 32 courses of FOLFIRI, 10 courses of CapeOX + Bmab, and 34 courses of LV5FU2 + Bmab, radiographic examination revealed complete response (CR) of the rectal tumor, and low anterior resection of the rectum was carried out. Since pathological examination showed no viable cancer cells in any specimen, the patient was considered to have achieved a CR from a pathological standpoint.

[A case of pancreatic cancer with local recurrence and liver metastases eight years after surgery].

Here we report a rare case of late recurrence of pancreatic cancer 8 years after surgery. A woman in her mid-fifties was hospitalized for examination of epigastralgia. Computed tomography (CT) revealed a 4 cm nodule at the pancreatic head with suspected invasion of the superior mesenteric vein. She underwent pancreaticoduodenectomy with wedge resection of superior mesenteric vein and intraoperative radiation therapy. Pathological findings showed moderately differentiated tubular adenocarcinoma and T3N1M0, Stage IIB according to The Union for International Cancer Control (UICC) TNM classification. As adjuvant chemotherapy, 56 courses of gemcitabine (GEM) were administered in 3.5 years. Because of long-term use of GEM, common terminology criteria for adverse events (CTCAE) Grade 3 anemia occurred, and chemotherapy was discontinued. Tumor markers were evaluated every month and CT scans were taken every 6 months for 5 years. Subsequently, CT was performed annually. The patient was hospitalized for high-grade fever, 8.5 years after surgery. CT, magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) detected local recurrence with liver metastases. GEM was administered again, but was ineffective. The patient died 9 years after surgery. In conclusion, even if long-term survival is achieved in pancreatic cancer, follow-ups should not be stopped.

[Two cases of advanced gastric cancer achieved pathological complete response by preoperative chemotherapy with S-1 plus weekly low-dose CDDP].

We report 2 cases of resectable advanced gastric cancer who achieved pathological complete response by preoperative chemotherapy with S-1 plus weekly low-dose cisplatin (CDDP). S-1 (80 mg/m²)was administered consecutively for 21 days followed by 14 days' rest, with CDDP (25mg/m²) injected on days 1, 8, and 21. Case 1: A man in his 70s diagnosed with cStage III gastric cancer with lymph node metastases received 2 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph node dissection. Case 2: A man in his 60s diagnosed with cStage III gastric cancer with lymph node metastases received 4 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph-node dissection. In both cases, postoperative pathological examination revealed no cancer cells in the resected stomach and lymph nodes. The therapeutic effect of preoperative chemotherapy was assessed as Grade 3. With this regimen, we accomplished preoperative chemotherapy successfully without inpatient care. This regimen can be a promising option as preoperative chemotherapy for advanced gastric cancer.

Photoreceptor impairment and restoration on optical coherence tomographic image.

With recent development of spectral-domain optical coherence tomography (SD-OCT), the pathological changes of retina can be observed in much greater detail. SD-OCT clearly delineates three highly reflective lines in the outer retina, which are external limiting membrane (ELM), photoreceptor inner and outer segment (IS/OS) junction, and cone outer segment tips (COST) in order from inside. These lines can serve as hallmarks for the evaluation of photoreceptor condition. In retinitis pigmentosa (RP) leading to photoreceptor degeneration, the ELM, IS/OS, and COST lines are shortened with the progression of the disease. In addition, shortening of the ELM, IS/OS and COST lines is significantly associated with each other. The line length is longest in the ELM, followed by the IS/OS, and COST, suggesting that retinal layer becomes disorganized first at the COST, followed by the IS/OS and finally the ELM. This finding is consistent with the previous report that the earliest histopathological change in RP is a shortening of the photoreceptor outer segments. On the other hand, retinal layer becomes restored first at the ELM, followed by the IS/OS and finally the COST after macular hole surgery. There may be a directionality of photoreceptor impairment or restoration on optical coherence tomographic image.

[A 5-year survival case of locally advanced cancer of the pancreatic body treated by distal pancreatectomy with en bloc celiac axis resection after neoadjuvant chemoradiation therapy].

A 59-year-old man was diagnosed with locally advanced cancer of the pancreatic body, involving the nerve plexus around the celiac axis, the common hepatic artery, and the splenic artery. He was treated with a combination of irradiation (2 Gy/day, total 24 Gy) and 600 mg/m2 of gemcitabine(GEM)biweekly. The tumor size and the involved plexus area were not diminished, but CA19-9 was reduced by half. Distal pancreatectomy with en bloc celiac axis resection(DP-CAR)was performed. The histological findings indicated extensive invasion into the nerve plexus, including that adjacent to the stump of the pancreas, and thus the R classification was R1. After surgery, 1,000 mg/m2 of GEM was administered biweekly. The chemotherapy has been performed for 5 years to prevent local and systemic recurrence. No recurrence has been found 5 years after surgery. Multidisciplinary treatment, combined with neoadjuvant chemoradiation therapy, curative-intent resection, and postoperative chemotherapy is important for effective treatment of locally advanced pancreatic cancer.

Expression of promyelocytic leukemia protein and vascular endothelial growth factor in aqueous humor and vitreous fluid in patients with proliferative diabetic retinopathy.

AIMS: To examine the expression of promyelocytic leukemia protein (PML) in the eye of proliferative diabetic retinopathy (PDR) patients. METHODS: PML mRNA levels were measured in proliferative membranes from 12 PDR patients and idiopathic epiretinal membranes from 5 control patients by quantitative RT-PCR. Protein levels of PML and vascular endothelial growth factor (VEGF) in aqueous humor and vitreous fluid samples from 34 PDR patients and 38 control patients were determined using ELISA. RESULTS: The PML mRNA expression levels in membrane samples, and the PML protein concentrations in aqueous humor and vitreous fluid samples were significantly lower in PDR patients than control patients. We observed a statistically significant inverse correlation between the concentrations of PML and VEGF in the aqueous humor and vitreous fluid of PDR patients. CONCLUSION: PML may be a good candidate as a diagnostic marker and a therapeutic agent for PDR.

Aggressive retinal astrocytoma associated with tuberous sclerosis.

We report the case of a patient with an aggressive retinal astrocytoma accompanied with macular edema and neovascular vessels, who was initially treated with intravitreal bevacizumab injections. A 24-year-old male presented to our clinic complaining of visual disturbance in his right eye. At 8 years of age, he had been diagnosed as having tuberous sclerosis complex. Fundus examination demonstrated a retinal tumor accompanied with marked neovascular vessels on the surface, retinal hemorrhage, and macular edema. After six monthly intravitreal bevacizumab injections, fundus examination demonstrated marked regression of the macular edema and neovascular vessels. Two months later, a vitreous hemorrhage developed which necessitated pars plana vitrectomy. After additional intravitreal bevacizumab injection for preventing intraoperative bleeding, vitrectomy with endophotocoagulation for the tumor was performed. The vitreous sample was obtained during vitrectomy, and we measured the vascular endothelial growth factor concentration by enzyme-linked immunosorbent assay. The surgically removed epiretinal neovascular membrane and biopsied retinal tumor expressed vascular endothelial growth factor, although several intravitreal bevacizumab injections led to a vitreous vascular endothelial growth factor concentration of undetectable levels. The clinical course and immunohistochemical analyses indicate that intravitreal bevacizumab monotherapy may have been insufficient to treat the aggressive retinal astrocytoma with macular edema and that laser photocoagulation or photodynamic therapy for the tumor should be considered following intravitreal bevacizumab injection in such cases.

A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats.

The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1(IIIB) and HIV-1(BaL) as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1(IIIB) activity, whereas fusion inhibitors showed both anti-HIV-1(IIIB) and anti-HIV-1(BaL) activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, "phenotypic drug evaluation", may be applicable for the evaluation of various antiviral drugs in vivo.