Hymenolepis microstoma: Effect of the mouse bile duct tapeworm on the metabolic rate of CF-1 mice

The metabolic rate of uninfected Mus musculus (CF-1 strain) at 30 C was 1.668 ± 0.032 ccO₂/g/hr (mean ± SE, n = 35). At 2 days postinfection (PI)the metabolic rate of infected mice was 2.64 ± 0.15 ccO₂/g/hr (n = 6), or 58% higher than that of uninfected control mice. Between 2 and 8 days PI there was a steady decrease in the metabolic rate of infected mice, and by Day 15 PI the metabolic rates of infected and uninfected mice were the same. Since gross histopathological changes (e.g., fibrosis of the bile duct and liver) in infected mice are not evident until Day 4 or 5 PI, the increased metabolic rate during the early stage of infection may be a direct response of the mouse to excretory (secretory) products of the developing parasite.     

不同周龄Balb／c小鼠脏器质量及其变化趋势分析

目的：测定不同周龄Balb／c小鼠主要脏器质量、脏器系数,并进行比较。方法：取120只3周龄、5周龄、7周龄的Balb／c小鼠,雌雄各半,精确测量小鼠体重和主要脏器质量,计算脏器系数。结果：①雌性与雄性Balb／c小鼠脏器质量相比较：3周龄时肝、脾有显著差异（P〈0．05）;5周龄时肝有非常显著差异（P〈0．01）,脾、肺有显著差异（P〈0．05）;7周龄时肝、肺及双肾有非常显著差异（P〈0．01）,心、脾有显著差异（P〈0．05）。②雌性与雄性Balb／c小鼠脏器系数相比较：3周龄时肝、脾有显著差异（P〈0．05）;5周龄时肝、脾有非常显著差异（P〈0．01）,膀胱有显著差异（P〈0．05）;7周龄时肺、双肾有非常显著差异（P〈0．01）,脾、膀胱有显著差异（P〈0．05）。结论：随着周龄的增长,Balb／c雌、雄性小鼠之间,存在差异的脏器也在增多。     

Hymenolepis microstoma: histopathological changes in mice maintained at different environmental temperatures

Livers of uninfected mice maintained at 5 C did not differ histologically from mice kept at 21 C, but the hepatocytes of mice kept at 35 C were depleted of glycogen. Regardless of temperature, infection with a single Hymenolepis microstoma induced inflammatory changes in the livers of all mice. However, the degree of histopathology was less in mice kept at 21 C than in mice at 5 C or 35 C. Infected mice in the hot and cold environments developed necrotic lesions in their liver parenchyma. Livers of mice kept at 35 C contained many foreign body giant cells. Temperature had no histological effect on the common bile duct, but in all infected mice there was a pronounced thickening of the bile duct wall due to intensive infiltration of the submucosa with fibrous connective elements and inflammatory leucocytes.     

Hepatic homing of mononuclear inflammatory cells isolated during murine chronic graft-vs-host disease

Liver injury in murine chronic graft-vs-host disease (CGVHD) to minor histocompatibility Ag, B10.D2----BALB/c (600 rad), is characterized by mononuclear cell inflammation and necrosis of interlobular bile ducts. Bile duct destruction in this model is similar to that which occurs in human CGVHD, late liver transplant rejection, and primary biliary cirrhosis. This model provides a unique opportunity to isolate mononuclear inflammatory cells from the liver during CGVHD, study their functions, and investigate the immunologic mechanisms responsible for bile duct destruction. In the present study, we compared the in vivo organ homing of mononuclear inflammatory cells (MC) isolated from the liver and spleen during the course of CGVHD. MC isolated from the liver showed a progressive increase in homing to the livers of BALB/c mice from day 7 through 42. In contrast, the hepatic homing of MC isolated from the spleen peaked at day 21 and subsequently declined. CGVHD spleen MC showed a progressive increase in homing to the spleen of BALB/c mice whereas CGVHD liver MC showed no change over time. Homing to other organs was negligible. The hepatic and splenic homing of MC isolated during CGVHD was significantly greater in BALB/c (host) mice than in B10.D2 (donor) mice. Autoradiography was used to determine the intrahepatic sites at which CGVHD liver MC accumulate after i.v. injection into BALB/c mice. The results indicated that MC isolated from the liver when bile duct inflammation is most intense accumulate preferentially in hepatic portal spaces in close proximity to interlobular bile ducts. These results suggest that hepatic homing by CGVHD liver MC is specific for minor histocompatibility Ag expressed on host biliary epithelial cells. These data support the hypothesis that bile duct destruction in murine CGVHD is mediated by MC that are sensitized to minor histocompatibility Ag expressed by host biliary epithelial cells.     

Entamoeba histolytica: antibody responses and lymphoreticular changes in gerbils (Meriones unguiculatus) in response to experimental liver abscess and amebic extract infection

Antibody responses and histological changes in hepatic lymph nodes and spleen of gerbils (Meriones unguiculatus) during the course of experimental hepatic amebiasis (5-60 days), or in those injected with extracts of Entamoeba histolytica, are described. Lymph node and spleen responses in infected animals paralleled the proliferation of the amebic liver abscess. However, spleen follicle responses were similar in animals that received low or high doses of the amebic extract and differed histologically from those with amebic liver abscess. Liver abscesses, up to 30 days postinfection (pi), doubled in weight between 10 and 15 and between 20 and 30 days pi. Early changes (10 days pi) in the lymphoreticular tissues were characterized by increased size and weight of the organs, hyperplastic follicles, and blastogenesis in the T-dependent areas. At 20 and 30 days pi, the size of spleen follicles increased and there was depletion of lymphocytes from the periarterial area (PAA), as well as gross extension of the red pulp, accompanied by extramedullary erythropoiesis and megakaryocytosis. The paracortical areas (PCA) of lymph nodes were depleted of lymphocytes and histiocytosis throughout the organ, and there was intense plasma cell activity in the medulla. At 60 days pi, lymphocyte repopulation was noted in the PCA and PAA; germinal centers were depleted of blast cells and the spleen red pulp had contracted. Antiamebic antibody titers were low throughout the infection. Changes in the cellularity of the lymphoid organs are discussed in relation to the proliferation of the amebic liver abscesses in infected animals and in those which were injected with the amebic extract.     

Schistosomatium douthitti: biochemical and morphological effects of an experimental infection in mice

The pathophysiological changes that occur in mice experimentally infected with Schistosomatium douthitti were studied. Male ICR mice, 6-8 weeks in age, were exposed to 100 cercariae of S. douthitti from infected snails (Lymnaea catascopium) and sacrificed weekly for a total of 13 weeks. Liver homogenates, serum samples, and histological sections of liver tissue were examined. Results showed that body weights of animals with prepatent infections were higher than those of corresponding controls. After patency, which occurred at 5 weeks, body weights were lower and liver weights were higher resulting in significantly increased liver weight/body weight ratios. Hematocrit values declined progressively in patent infections. Total cholesterol in liver was generally higher in the parasitized groups reaching significance during patency. Values rose with age in both control and parasitized groups, but sooner in the latter. Free cholesterol was increased in the liver of animals with patent infections. Total lipid content of the liver was reduced in the infected animals throughout the study. Both liver glycogen and serum glucose levels in the infected animals rose over the control values. The activity of alkaline phosphatase (E.C.3.1.3.1) was elevated in liver tissue of infected mice. Glutamic-pyruvic transaminase (E.C.2.6.1.2) activity was higher in serum but lower in the livers of animals harboring patent infections. Total bile salt concentration in parasitized animals did not differ appreciably from control values; however, gallbladders were enlarged five times in the infected animals. Histologically, liver sections from infected mice showed granulomas in various stages of formation and degeneration. Granulomas contained from 1 to 40 schistosome eggs. After 6 weeks of infection, granulomas were characterized by many neutrophils and monocytes. Few lymphocytes and eosinophils were present. As the granulomas developed, fibroblasts and connective tissue became more prominent. Glycogen deposits were observed surrounding granulomas and were increased in older infections. Adult worms contained abundant amounts of glycogen and cholesterol in their parenchymal tissues.     

不同周龄Balb/c小鼠脏器质量及其变化趋势分析

目的:测定不同周龄Balb/c小鼠主要脏器质量、脏器系数,并进行比较。方法:取120只3周龄、5周龄、7周龄的Balb/c小鼠,雌雄各半,精确测量小鼠体重和主要脏器质量,计算脏器系数。结果:①雌性与雄性Balb/c小鼠脏器质量相比较:3周龄时肝、脾有显著差异(P0.05);5周龄时肝有非常显著差异(P0.01),脾、肺有显著差异(P0.05);7周龄时肝、肺及双肾有非常显著差异(P0.01),心、脾有显著差异(P0.05)。②雌性与雄性Balb/c小鼠脏器系数相比较:3周龄时肝、脾有显著差异(P0.05);5周龄时肝、脾有非常显著差异(P0.01),膀胱有显著差异(P0.05);7周龄时肺、双肾有非常显著差异(P0.01),脾、膀胱有显著差异(P0.05)。结论:随着周龄的增长,Balb/c雌、雄性小鼠之间,存在差异的脏器也在增多。     

Ganglioside expression in tissues of mice lacking the tumor necrosis factor receptor 1

This study presents a comparative analysis of gangliosides from lymphoid (spleen and thymus) and other tissues (brain, liver, lung, muscle) of C57BL/6 mice homozygous (-/-) and heterozygous (+/-) for the tumor necrosis factor receptor 1 (TNFRp55). Quantitative and qualitative differences in the expression of the lipid-bound N-acetylneuraminic (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) and of various ganglioside biosynthesis pathways were detected between the tissues of the TNFRp55 -/- and the control TNFRp55 +/- mice. Sialic acid profiles showed a strong decrease in the absolute amount of sialic acids (Neu5Ac + Neu5Gc) in the lungs and thymus of homozygous (1.41 and 0.3 ng/mg wet weight, respectively) compared with control heterozygous animals (7.18 and 2.05 ng/mg wet weight, respectively). Considerable differences of Neu5Ac/Neu5Gc ratios in the lungs, muscle, spleen, and thymus were also detected. The gangliosides GM3(Neu5Ac) and GM3(Neu5Gc) were the dominant gangliosides in the lungs of the control animals, whereas the knockout mice almost completely lacked these structures in this organ. Reduced expression of GM1b-type gangliosides (GM1b and GalNAc-GM1b) was also found in the lungs, spleen, and thymus of the TNFRp55 knockout mice. On the other hand, neolacto-series gangliosides were more abundant in the lungs, brain, and muscle of the knockout mice, whereas their expression in the liver, spleen, and thymus was similar in both groups of animals. This study provides in vivo evidence that TNF signaling via the TNFRp55 is involved in the acquisition of a distinct ganglioside assembly in different mouse organs. TNFRp55 signaling seems to be especially important for the activation of the GM1b-type ganglioside biosynthetic pathway that is a unique characteristic of the mouse lymphoid tissues.     

Protective effects of thymoquinone against cholestatic oxidative stress and hepatic damage after biliary obstruction in rats

The aim of this study was to examine the preventive and therapeutic effects of thymoquinone (TQ) against cholestatic oxidative stress and liver damage in common bile duct ligated rats. A total of 24 male Sprague–Dawley rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received TQ; each group contain 8 animals. The rats in TQ treated groups were given TQ (50 mg/kg body weight) once a day orally for 2 weeks starting 3 days prior to BDL operation. To date, no more biochemical and histopathological changes on common bile duct ligated rats by TQ treatment have been reported. The application of BDL clearly increased the tissue hydroxyproline (HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme [superoxide dismutase (SOD), glutathione peroxidase (GPx)] activities. TQ treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced of SOD, and GPx enzymes in the tissues. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with TQ attenuated alterations in liver histology. The immunopositivity of alpha smooth muscle actin and proliferating cell nuclear antigen in BDL were observed to be reduced with the TQ treatment. The present study demonstrates that oral administration of TQ in bile duct ligated rats maintained antioxidant defenses and reduces liver oxidative damage and ductular proliferation. This effect of TQ may be useful in the preservation of liver function in cholestasis.     

Tissue alterations in Microtus montanus chronically infected with Trypanosoma brucei gambiense

Changes in liver, spleen, kidneys, heart, and brain are reported for Microtus montanus chronically infected with Trypanosoma brucei gambiense. An increase in body weight of infected animals was attributable to a significant increase in total mass of spleen, liver and kidney. Cellular infiltrate consisting primarily of lymphocytes and plasma cells was observed in all organs and was particularly evident in intralobular connective tissue of the liver, adipose tissue of the hilum, and adjacent medullary region of the kidney, spleen, and the meninges. Disruption of normal metabolism and the pathological changes observed in liver and kidney suggest that the survival of trypanosome-infected voles is dependent largely on the physiological response occurring in these organs.     

Hepatic coccidiosis in the goat

Coccidial oocysts were seen in the bile from five goats infected with coccidia either naturally or artificially. The oocysts measured on average 21.3 by 18.3 microns and resembled those of Eimeria ninakohlyakimovae. Livers and gall bladders of infected animals showed various degrees of histopathological changes. In the worst case, bile had a thick consistency and contained blood and necrotic debris. Apart from those in the bile, oocysts were seen in liver smears and in the centrilobular vein in two histological sections. Forms resembling meronts and measuring on average 200 by 147 microns were seen in sections of bile duct.     

Histopathology of Trypanosoma (Trypanozoon) evansi infection in bandicoot rat. I. visceral organs

Experimental infection of Trypanosoma (Trypanozoon) evansi in Bandicota bengalensis produces an acute disease course leading to untimely death of the bandicoot rat. The sequential alteration of liver, spleen, lung, kidney, and heart was studied on the 5th, 8th, 12th, and 14th days postinoculation. The rats showed inflammatory, degenerative, and necrotic changes in these organs. In liver, pseudolobule formation, necrosis and hemorrhage within the sinusoids, and fatty degeneration of hepatic cells were the predominant histopathological changes. The changes were destructive and irreversible. In spleen giant cells aggregation and granulomatous lesion, i.e., accumulation of histiocytes, were the protective changes, whereas tissue and cell damage indicated irreversible degeneration. The gradual development of intrabronchus inflammation, aggregation of inflammatory cells around the alveoli, congestion of bronchioles, septal edema, atrophy of alveolar walls, migration of macrophages, and emphysema were the histopathological changes noticed in the lungs of the infected rats. The affected kidney showed infiltration of lymphocytes, hemorrhage in the interlobular space, and glomerulitis as the irreversible and destructive changes in the rats. There was degeneration of myocardium in the hearts of the rats. The histopathological changes in these organs are compared with those studied in surra, human sleeping sickness disease, and African trypanosomiasis. Possible mechanisms for these histological changes in the visceral organs are discussed.     

Bile duct hyperplasia in mice infected with Schistosoma mansoni

Schistosoma mansoni releases large amounts of proline into the hepatoenteric circulation. Because proline release has been linked to bile duct hyperplasia in fascioliasis, the current investigation tested the possibility that such hyperplasia might occur in schistosomiasis. The lumenal perimeter and wall thickness in bile ducts was compared between infected and uninfected mice. In those harboring 5 week old S. mansoni infections there was a 180% increase in the lumenal perimeter of the duct (P<0.001) and a 580% increase in the thickness of the duct wall (P<0.001). These results tend to support data linking proline to bile duct and liver fibroblast proliferation.     

Eosinophilia, granuloma formation, migratory behaviour of second stage larvae in murine Toxocara canis infection. Effect of the inoculum size

Experimental infection of mice with Toxocara canis provides one of the best models for immunological and pathological studies of the visceral larva migrans syndrome. Blood eosinophilia, the migratory behaviour of second stage larvae and granuloma formation were studied in Swiss mice infected with Toxocara canis. Eosinophilia, spleen, liver and lung indexes were followed during a primary infection with different inoculum sizes (500 and 1500 eggs) while the migratory behaviour of larvae was studied in a primary infection with 1500 eggs over a period of 4 months. In mice infected with three challenges of 1500 eggs in order to elicit a strong inflammatory reaction in the tissues, a histopathological study was carried out. The results showed that eosinophilia, spleen and lung indexes (but not the liver index) were influenced by the parasite inoculum size. The migratory behaviour study showed that larval recovery was maximal three days post-infection, from the liver and lungs; the peak recovery from the skeletal muscles and brain being on days 15 and 30 post-infection, respectively. The histopathological study revealed the formation of granulomas in all the tissues examined (liver, lungs, kidneys, spleen, lymph nodes, myocardium etc.) but not in nervous tissue or in the retina of the eye. Granulomas in the lungs were larger than those found in the liver. The implications of these results are discussed considering host-parasite inter-relations.     

高海拔地区内毒素致绵羊多脏器功能障碍综合征的病理学改变

目的研究高海拔地区内毒素致绵羊多脏器功能障碍综合征（MODS）的病理学变化特征。方法将16只绵羊随机分为2组,中度海拔组和高海拔组,按相同的剂量静脉给予内毒素（6μg/kg）制作MODS模型,24h后麻醉处死绵羊,观察主要脏器的病理学变化。结果中度海拔和高海拔MODS组绵羊肺脏、肝脏、脾脏、肠粘膜均出现明显炎性改变,高海拔MODS组绵羊肺脏、肝脏病理学评分明显高于中度海拔MODS组。结论高海拔地区MODS的病理损伤较中度海拔明显加重。     

Trypanosoma brucei brucei: A comparison of gene expression in the liver and spleen of infected mice utilizing cDNA microarray technology

Trypanosoma brucei brucei, the infectious agent of the disease known as Nagana, is a pathogenic trypanosome occurring in Africa, where it causes significant economic loss to domesticated livestock. Although many studies on the histopathology of organs of mice infected with T. b. brucei have been reported, little work has been done regarding gene expression in these organs in infected mice. In this paper, we describe the use of cDNA microarray to determine gene expression profiles in the liver and spleen of mice infected with T. b. brucei (STIB 920) at peak parasitaemia (12 days after infection). Our results showed that a total of 123 genes in the liver and 389 genes in the spleen were expressed differentially in T. b. brucei infected mice. In contrast, however, in an acute infection in mice caused by Trypanosoma brucei evansi, a species genetically related to T. b. brucei, 336 genes in the liver and 190 genes in the spleen were expressed, differentially, indicating that the liver of mice was more affected by the acute T. b. evansi infection whilst the spleen was more affected by the subacute T. b. brucei infection. Our results provide a number of possible reasons why mice infected with T. b. evansi die sooner than those infected with T. b. brucei: (1) mice infected with T. b. evansi may need more stress response proteins to help them pass through the infection and these are probably excessively consumed; (2) proliferating cell nuclear antigen was more down-regulated in the liver of mice infected with T. b. evansi, which indicated that the inhibition of proliferation of hepatocytes in mice infected with T. b. evansi might be more severe than that in T. b. brucei infection; and (3) more hepatocyte apoptosis occurred in the mice infected with T. b. evansi and this might be probably the most important reason why mice died sooner than those infected with T. b. brucei. Studies of the changes in the gene expression profile in the liver and spleen of mice infected with T. b. brucei may be helpful in understanding the mechanisms of pathogenesis in Nagana disease at the molecular level. By comparing the gene profiles of the liver and spleen of mice infected with T. b. brucei with T. b. evansi, we have identified a number of factors that could explain the differences in pathogenesis in mice infected with these two African trypanosomes.     

Effect in rats of simultaneous prenatal exposure to ochratoxin A and aflatoxin B1. II. Histopathological features of teratological anomalies induced in fetuses

The histopathological features of various abnormalities induced by different doses of ochratoxin A (OA), aflatoxin B1 (AFB1), and their combination in rat fetuses were studied. The pregnant Wistar rats were orally treated during 6-15 gestation days with different doses of OA (0.125, 0.25, 0.50, 0.75 mg/kg), AFB1 (0.125, 0.25, 0.50, 1.00 mg/kg), and their combination (0.125+0.125, 0.25+0.50, 0.50+0.25 mg/kg). The fetal sections passing through liver, kidney, brain, heart, and eyes were selected from the fetuses given visceral examination representing each litter. The selected sections were processed for paraffin embedding, stained with H and E, and examined by light microscopy. The histological examination of the fetal organs revealed that OA, AFB1, and their combination treatments caused variable changes in internal organs. In the case of OA, the incidence of pathological lesions liver, kidney, brain, and eye lesions was high, whereas in AFB1 treatment, liver, brain, kidney, and heart were affected. The incidence of heart lesions, especially valvular defects, increased in the combination groups. Bile duct proliferation/new bile duct formation, defective ossification of cranial bones, exposure of the brain to the exterior, hypoplasia of cerebellum, and retinal defects observed in OA treatment and spinal cord defects in addition to liver, kidney, and brain changes observed in AFB1 were less severe in the combination groups. The present study indicates that the occurrence of brain, kidney, and liver lesions in combination treatment was less than in either individual treatment suggesting antagonism of OA-induced teratogenic effects by AFB1. The indication of subtle lesions due to an interference with normal development and arrest of differentiation in various internal organs observed in the present study suggests that microscopic examination of the tissues can provide additional useful information to a developmental toxicity study.     

Melatonin reduces oxidative damage and increases survival of mice infected with Schistosoma mansoni

The tropical parasite Schistosoma mansoni causes granulomatous inflammation after its eggs lodge in hepatic portal capillaries. In vitro studies indicate that the host's response involves the production of reactive oxygen species, although whether this occurs in vivo at the site of the infection is unknown. The role of oxidative processes in mice infected with S. mansoni was investigated in the current study using the antioxidant melatonin. In Experiment 1, the survival rate of infected mice with and without daily melatonin (10 mg/kg) administration was determined. After 56 d, 25 of 25 infected mice that were diluent treated had died. In contrast, 22 or 25 infected mice (88%) given melatonin were still alive at 56 d. Of these 22 surviving mice, melatonin injections were continued in 11 while the 11 others were switched to diluent. Within 10 d, 11 of 11 diluent-injected mice that were infected with S. mansoni were dead while 6 of 11 melatonin-treated mice survived. In Experiment 2, S. mansoni-infected mice were treated for 30 d with either melatonin or diluent. Uninfected, untreated mice served as controls. In these mice, the levels of lipid peroxidation (LPO) products, vitamin E, nitric oxide (NO), glutathione (GSH), and superoxide dismutase (SOD) activity in the liver, kidney, and spleen were measured. In the serum, cholesterol levels and liver damage (alkaline phosphatase (ALP), aspartate transaminases (AST), total protein, and albumin) were monitored. In addition, peroxynitrite anion (ONOO(-)) in the liver and kidney and inducible nitric oxide synthase (iNOS) in the spleen were immunocytochemically localized. Also, histopathological changes in the liver, kidney, and spleen were examined. The results documented increased LPO and NO levels and decreased vitamin E, GSH, and SOD activity in the liver, kidney, and spleen of S. mansoni-infected mice. Also, there was an increase in serum cholesterol and evidence of liver damage in the infected mice. Immunohistochemical results indicated positive staining of ONOO(-) in the liver and kidney and positive iNOS staining in the spleen of S. mansoni-infected mice. Histopathological observations revealed granuloma formation in the liver with eosinophil infiltration, a large number of megakaryocytes in the spleen, and degeneration with necrotic cells in some tubules of the kidney cortex in the infected mice. Melatonin administration after S. mansoni infection prevented most of the previously described changes. These results suggest that oxidative processes occur at the site of inflammation and are involved in the damaging effects of schistosomiasis and indicate that free radicals may be a major component of the disease. Likewise, melatonin, presumably due to its antioxidant and free radical scavenging activity, is highly protective against the pathological changes associated with schistosomiasis.     

Pathology of naturally occurring toxoplasma abortion and neonatal mortality in Black Bengal goat

Characteristic pathological lesions in Black Bengal goat abortions due to naturally occurring toxoplasmosis consist of focal inflammation of the placenta. No specific macroscopic changes were marked in other organs of the fetuses. The main microscopic changes were focal or diffuse infiltrations with round cells in the liver, brain and heart. These lesions were more common in the brain than in other organs. Toxoplasma organisms were demonstrated in these organs as single trophozoites or within the cyst. No characteristic gross or histological changes were demonstrated in lymph nodes, spleen, lung and kidney. These results could be useful for histopathological diagnosis of toxoplamosis in Black Bengal goats.     

Evaluation of the experimental pathogenicity of some Cryptococcus species in normal and cyclophosphamide-immunodepressed mice

The pathogenic potential of distinct Cryptococcus species has been evaluated in mice rendered leukopenic by one or two injections of the potent immunosuppressive drug cyclophosphamide (Cy). Pathogenicity assessment included enumeration of viable cryptococcal cells in animal organs and histopathological observations. It was found that putatively non-pathogenic species of Cryptococcus, in particular C. cereanus and C. albidus, showed significant lethality for Cy-treated mice. In Cy-immunodepressed mice, challenged with the infectious cryptococcal cells two days after pharmacological treatment, a significant decrease of LD50 (equivalent to at least one order of magnitude) was observed for all Cryptococcus species. However, the pathogenicity enhancement due to Cy immunodepression was greater with C. neoformans. In all cases, brain and kidney were the most invaded tissues as also evidenced by histopathological examination, which showed the typical cystic lesion. All the observations made point to the conclusion that the pathogenic potential, for the immunomodulated host, of Cryptococci other than C. neoformans is significant being quantitatively and not qualitatively different from that of C. neoformans, as evidenced by a similar organotropism and similar type of histological lesions in the target organs (brain and kidney).