Ulcerative dermatitis in C57BL/6 mice exhibits an oxidative stress response consistent with normal wound healing

Ulcerative dermatitis (UD) is a common syndrome of unknown etiology that results in profound morbidity in C57BL/6 mice and lines on a C57BL/6 background. The lesions are due to severe pruritus-induced self-trauma, progressing from superficial excoriations to deep ulcerations. UD may be behavioral in origin, with ulcerative lesions resulting from self-mutilating behavior in response to unresolved inflammation or compulsion. Alternatively, abnormal oxidative damage may be a mechanism underlying UD. To evaluate whether UD behaves similarly to normal wounds, consistent with a secondary self-inflicted lesion, or is a distinct disorder with abnormal wound response, we evaluated expression levels of genes representing various arms of the oxidative stress response pathway UD-affected and unwounded C57BL/6J mice. No evidence indicated that UD wounds have a defect in the oxidative stress response. Our findings are consistent with an understanding of C57BL/6 UD lesions as typical rather than atypical wounds.     

Some dental traits of Diaguitas Indian skulls

Dental characteristics were studied on 60 skulls that belong to a population of Diaguitas Indians of approximately the Tenth Century. Mesiodistal crown diameters of permanent teeth were as follows: central incisors (8.77 mm), lateral incisors (7.23 mm), canines (8.40 mm), first maxillary molars (10.77 mm), second maxillary molars (10.71 mm), first mandibular molars (11.13 mm), and second mandibular molars (10.17 mm). Also determined was the frequency of shovel shaped incisors (80.30%), groove and cusp patterns of mandibular molars (Y5 73.40%), groove and cusp patterns of maxillary molars (H4 87.25%), and mesiopalatal version of maxillary incisors (66.20%). No skull showed Carabelli's cusp. The findings were compared with those for different populations past and living. The results suggest that the affiliation of the population analyzed was mongoloid.     

Permanent tooth emergence in Gujjars of Punjab, India.

Patterns of permanent tooth emergence in Gujjars were studied in a cross-sectional sample of 483 children ranging in age from 6 to 13 years. Females were markedly advanced in permanent tooth emergence times over males, but no such sex differences were observed in sequence of emergence. Differences between median emergence times of right and left side antimers were significant for only 4 of 28 instances (14.29%), namely central incisors, mandibular first molars in males and lateral maxillary incisors in females. In general mandibular teeth except premolars tended to emerge earlier than their maxillary counterparts. The quiescent period between first and second tooth emergence stages was longer in males than in females. Mandibular depth and morphological facial length were very significantly correlated (p < 0.01) with the number of permanent teeth present in the oral cavity.     

Smad3 is required for enamel biomineralization

Smad3 is an intracellular signaling molecule that mediates the signal from transforming growth factor-beta (TGF-beta) and activin receptors. In this study, we reveal hypomineralized enamel in mice with the targeted deletion of the Smad3 gene. The Smad3 (-/-) mice had chalky white incisor enamel, while the enamel of the wild-type or Smad3 (+/-) mice was yellow-brown. Histological analysis of the undecalcified sections showed that the enamel thickness of the maxillary incisors in the Smad3 (-/-) mice was similar to that of the wild-type and Smad3 (+/-) mice while that the enamel of the maxillary molars in Smad3 (-/-) mice was disrupted in places. Microcomputed tomography (microCT) analysis revealed that the mineralization of the maxillary incisors and mandibular molars in the Smad3 (-/-) mice showed significant reduction in the degree of mineralization when compared to that of the wild-type and Smad3 (+/-) mice. Scanning electron microscopic (SEM) analysis of the mandibular incisors revealed that the enamel surface of the Smad3 (-/-) mice was irregular and disrupted in places and showed images similar to decalcified mature enamel. The histological analysis of the decalcified sections showed that distinct morphological changes in the ameloblasts at the secretory and maturational stages were not observed between the Smad3 (-/-) and Smad3 (+/-) or wild-type mice, while the enamel matrix was observed in the decalcified sections of the mandibular molars in the Smad3 (-/-) mice. These results suggested that Smad3 was required for enamel biomineralization, and TGF-beta and activin signaling might be critical for its process.     

Arch form,tooth size,and occlusomandibular kinesis in the Ceboidea

Correlations between dental morphology, arch configuration, and jaw movement patterns were quantitatively investigated in 23 ceboid species to elucidate integrative aspects of occlusal functional anatomy in an adaptive and evolutionary context. Differential maxillary-mandibular arch widths are primary in guiding lateral jaw movements. These movements are characterized according to their associated condylar shifts as either predominantly translatory or rotational. Predominantly translatory movements result from peripheral contact relationships between maxillary arches which are considerably wider posteriorly than their opposing mandibular arches. The greatest degree of mandibular movement is in the molar region in functional association with wide “primitive” maxillary molars, narrow mandibular molars, constricted maxillary intercanine widths, and narrow maxillary incisors. In contrast, predominantly rotational masticatory jaw movements result from differential arch widths which are greatest in the maxillary canine and incisor regions. Here most jaw movement is in the anterior segment and this is reflected in small maxillary-mandibular molar width differences, a high degree of premolarization, wide-set maxillary canine teeth, and wide maxillary incisors. Possible selectional factors in the putative evolution of rotational predominance in mastication from the more primitive translatory pattern are discussed.     

Role for MyD88, TLR2 and TLR9 but not TLR1, TLR4 or TLR6 in experimental autoimmune encephalomyelitis

The potential roles of TLRs in the cause and pathogenesis of autoimmune CNS inflammation remain contentious. In this study, we examined the effects of targeted deletions of TLR1, TLR2, TLR4, TLR6, TLR9, and MyD88 on the induction of myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) peptide/CFA/pertussis toxin-induced autoimmune encephalomyelitis. Although C57BL/6.Tlr1(-/-), C57BL/6.Tlr4(-/-) and C57BL/6.Tlr6(-/-) mice showed normal susceptibility to disease, signs were alleviated in female C57BL/6.Tlr2(-/-) and C57BL/6.Tlr9(-/-) mice and C57BL/6.Tlr2/9(-/-) mice of both sexes. C57BL/6.Myd88(-/-) mice were completely protected. Lower clinical scores were associated with reduced leukocyte infiltrates. These results were confirmed by passive adoptive transfer of disease into female C57BL/6.Tlr2(-/-) and C57BL/6.Tlr9(-/-) mice, where protection in the absence of TLR2 was associated with fewer infiltrating CD4(+) cells in the CNS, reduced prevalence of detectable circulating IL-6, and increased proportions of central (CD62L(+)) CD4(+)CD25(+)Foxp3(+) regulatory T cells. These results provide a potential molecular mechanism for the observed effects of TLR signaling on the severity of autoimmune CNS inflammation.     

Tooth eruption in Reeves' muntjac (Muntiacus reevesi) and its use as a method of age estimation (Mammalia: Cervidae)

The sequence of tooth eruption and replacement in Reeves' muntjac was determined from captive animals of known age. Pronounced sexual dimorphism is shown by the permanent upper canine which in the male is large, tusk-like and is used as a weapon. The upper canine was the first deciduous tooth to be replaced in males, at approximately 21 weeks of age, compared with 53–57 weeks in the female. The permanent mandibular teeth erupted in the order: molars, first and second incisors, premolars, third incisor and canine. The maxillary teeth erupted in the order: first molar, canine (in male), second and third molars, canine (in female), premolars. The full complement of 34 functional permanent teeth was attained by 83–92 weeks of age.     

The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development.

The gene for activin betaA is expressed in the early odontogenic mesenchyme of all murine teeth but mutant mice show a patterning defect where incisors and mandibular molars fail to develop but maxillary molars develop normally. In order to understand why maxillary molar tooth development can proceed in the absence of activin, we have explored the role of mediators of activin signalling in tooth development. Analysis of tooth development in activin receptor II and Smad2 mutants shows that a similar tooth phenotype to activin betaA mutants can be observed. In addition, we identify a novel downstream target of activin signalling, the Iroquois-related homeobox gene, Irx1, and show that its expression in activin betaA mutant embryos is lost in all tooth germs, including the maxillary molars. These results strongly suggest that other transforming growth factor beta molecules are not stimulating the activin signalling pathway in the absence of activin. This was confirmed by a non-genetic approach using exogenous soluble receptors to inhibit all activin signalling in tooth development, which reproduced the genetic phenotypes. Activin, thus, has an essential role in early development of incisor and mandibular molar teeth but this pathway is not required for development of maxillary molars.     

Morphoregulation of teeth: modulating the number, size, shape and differentiation by tuning Bmp activity

During development and evolution, the morphology of ectodermal organs can be modulated so that an organism can adapt to different environments. We have proposed that morphoregulation can be achieved by simply tilting the balance of molecular activity. We test the principles by analyzing the effects of partial downregulation of Bmp signaling in oral and dental epithelia of the keratin 14-Noggin transgenic mouse. We observed a wide spectrum of tooth phenotypes. The dental formula changed from 1.0.0.3/1.0.0.3 to 1.0.0.2(1)/1.0.0.0. All mandibular and M3 maxillary molars were selectively lost because of the developmental block at the early bud stage. First and second maxillary molars were reduced in size, exhibited altered crown patterns, and failed to form multiple roots. In these mice, incisors were not transformed into molars. Histogenesis and differentiation of ameloblasts and odontoblasts in molars and incisors were abnormal. Lack of enamel caused misocclusion of incisors, leading to deformation and enlargement in size. Therefore, subtle differences in the level, distribution, and timing of signaling molecules can have major morphoregulatory consequences. Modulation of Bmp signaling exemplifies morphoregulation hypothesis: simple alteration of key signaling pathways can be used to transform a prototypical conical-shaped tooth into one with complex morphology. The involvement of related pathways and the implication of morphoregulation in tooth evolution are discussed.     

Association of relatively delayed emergence of mandibular molars with molar reduction and molar position

Among 234 children examined annually from age three to 20 years at the Burlington Growth Centre, there was statistically significant cooccurrence of early and late emergence sequences of the permanent first and second molars relative to the central incisors and second premolars in the same jaw and in both jaws. Alternatively, mandibular molar delay was not accompanied by corresponding maxillary molar delay, and the mandibular molars emerged later than the maxillary molars. This was strongly associated with Angle Class II malocclusion, indicating a relationship between relative time of emergence and relative position of opposing molars. Delay of the mandibular molar relative to the successional teeth or maxillary molars was associated with increased frequency of four cusped first and second molars and agenesis of third molars, indicating a tendency for co-occurrence of delay in timing of molar emergence with reduction in structure of the molars. These relationships were evident even though emergences were affected by early loss of a deciduous second molar which increased M1I1 and M2P2 sequences by earlier emergence of M1 and delayed emergence of P2.     

Schistosoma japonicum: Infection characteristics in mice of various strains and a difference in the response to eggs

Female mice of 12 inbred strains were exposed to 20–25 cercariae of Schistosoma japonicum and infection status determined at day 40 by counting numbers of adult worms, eggs in faeces and eggs in a segment of liver. Most mouse strains appeared to be ‘permissive’ hosts although at least one strain (129/J) was shown to be relatively resistant in terms of day 40 adult worm numbers. In a radioisotopic lung assay for sensitivity to eggs, and developed as a rapid means of assessing granuloma formation, CBA/H mice were shown to differ from C57BL/6 mice in being non-responders. Histological examination of lungs of sensitized CBA/H and C57BL/6 mice injected intravenously with eggs established that granuloma formation was much more intense in C57BL/6 than CBA/H mice. Preliminary indications are that infected CBA/H mice are also low anti egg circumoval precipitin (COP) responders. Analysis of immune responses to isolated egg antigens in these two strains, and identification of the antigens of eggs to which such responses are directed in C57BL/6 mice, should provide insights into immunological disease processes (such as granulomatous inflammation) in this model system of japonicum schistosomiasis.     

Origin of hematopoietic cells in a syngenous and semisyngenous focus of heterotopic hematopoiesis]

Heterotopic hemopoiesis foci were produced by the bone marrow of C57BL/6 or (CBA X C57BL)F1 mice grafted under the renal capsule of (CBAT6T6XC57BL)F1 mice, bearing the chromosomal translocation. The cytogenetic analysis of the hemopoietic cells in the foci 20 to 120 days after the transplantation showed that in 40% of the transplants only the recipient's hemopoietic cells proliferated, whereas the rest were mosaic and contained on the average less than 20% of donor's cells both in the syngeneic and in the semisyngeneic systems. These characteristics remained stable for at least 4 months. The data obtained suggest a single inflow of not less than 10 effective hemopoietic stem cells per graft. The clone stability indicated that during the steady-state hemopoiesis the cell exchange between various regions of the hemopoietic system was not great, if any.     

不同群系小鼠胚胎玻璃化冷冻保存技术的研究

利用 EFS40 ,二步法对近交系 C5 7BL/6、DBA/2和远交群 ICR小鼠囊胚玻璃化冷冻保存 ,并对冷冻后胚胎体内、外发育效果进行比较。结果表明 ,相同条件下鲜胚经培养 ,近交系 C5 7BL /6小鼠的囊胚发育率 ( 93% )与 ICR( 1 0 0 % )相比差异不显著 ( P>0 .0 5 ) ;而两近交系的囊胚孵化率明显低于 ICR( P<0 .0 1 )。 C5 7BL/6、DBA/2小鼠囊胚冷冻后发育率 ( 93% ,96% )和孵化率 ( 5 2 % ,46% )与各自对照组 ( 1 0 0 % ,1 0 0 %和 61 % ,62 % )相比均无显著差异 ( P>0 .0 5 ) ;并且与 ICR冷冻组发育率和孵化率 ( 94% ,5 3% )之间也无显著差异 ( P>0 .0 5 )。两近交系冻胚移植妊娠与各自对照组和 ICR冷冻组比较均无显著差异 ( P>0 .0 5 )。C5 7BL/6胚胎移植产仔率 ( 35 % )与对照组 ( 5 1 % )之间差异显著 ( P<0 .0 1 ) ,而 DBA/2胚胎移植产仔率 ( 4 7% )与对照组和 ICR冷冻组 ( 39% ,5 8% )相比差异不显著 ( P>0 .0 5 )。     

Disproportionate eruption of maxillary and mandibular incisors in the long-tailed ground squirrel

The surface of the maxillary and mandibular incisors of Spermophilus undulatus long-tailed ground squirrels, including those born in the current year and those that have hibernated (trapped one month or later after hibernation) is studied. The presence of daily growth increments on the incisors’ surface allows the evaluation of the eruption rate of the incisors; a specific change in the character of the growth increments corresponds to winter hibernation (hibernation zone), which serves as the time mark. Ratio between the eruption rates of the maxillary and mandibular incisors typical for rodents is found in young-of-the-year and some animals after hibernation. In these animals the eruption rate of the mandibular incisors is higher than the eruption rate of the maxillary incisors and can be taken as proportional to their length. In individuals that have hibernated and show proportional eruption of the incisors, the proportions of the total length of the incisor formed before hibernation zone are equal for the maxillary and mandibular incisors. In the individuals that also have hibernated and show the ratio between the total length of the maxillary and mandibular incisors typical for rodents, the eruption rate of the mandibular incisor is equal to or less than the eruption rate of the maxillary incisor and the proportion of the incisor formed before hibernation is greater in the mandibular incisor than in the maxillary. This disproportionate pattern of incisor eruption is not typical for rodents and is a result of inequal attrition of the maxillary and mandibular incisors, which ultimately results in the normal ratio of the total length of the maxillary and mandibular incisors.     

Formation of the permanent dentition in Arikara Indians: timing differences that affect dental age assessments

This report concerns one problem encountered with application of American white dental formation standards to age assessment of sub-adults of archaeological context. Dental ages for eight mandibular permanent teeth and maxillary central and lateral incisors of Arikara Indian immature skeletons were determined according to degree of crown or root mineralization. Ages assigned to the various teeth of the same individual were compared. They showed similarities as well as patterned differences. First premolar, second premolar, and mandibular incisor ages closely approximated one another. In relation to this complex, dental ages for maxillary incisors and mandibular second molars were older by 0.5 to 1.1 years. Developmental ages assigned to individuals on the basis of third molars showed relative advancement by more than 2 years. The systematic occurrence of these observations reflects more than just individual variability; it shows the presence of population differences in tooth-formation timing. Timing differences complicate assessment of dental ages needed for growth or demographic studies.     

Role of natural killer cells as immune effectors in encephalitis and demyelination induced by Theiler's virus

Infection of susceptible mice (SJL) with Theiler's murine encephalitis virus (TMEV) causes a biphasic disease characterized by gray matter inflammation followed by late chronic demyelination. The role of NK cells was studied in this model by using susceptible (SJL) or resistant (C57BL/10) mice. CNS TMEV titer were higher in SJL compared with C57BL/10 mice, correlating with a 50% lower NK cell activity in the SJL than in the C57BL/10 mice. When resistant (C57BL/10) mice were depleted of NK cells using either mAb NK1.1 or polyclonal anti-asialo-GM1, TMEV induced the development of diffuse encephalitis and meningitis early in the postinfection period (days 6 to 11). However, the second phase of TMEV-induced CNS disease (demyelination) was observed only in resistant C57BL/10 mice treated with anti-asialo-GM1. Experiments with beige/beige mice of C57BL/10 background showed a mild degree of gray matter inflammation but no demyelination. In conclusion, NK cells are critical effectors in protecting against TMEV-induced gray matter disease, whereas a different population of either NK1.1- NK cells, or other activated lymphocytes may be critical in resistance/susceptibility to demyelination.     

A dhfr-ts- Leishmania major knockout mutant cross-protects against Leishmania amazonensis.

E10-5A3 is a dhfr-ts- Leishmania major double knockout auxotrophic shown previously to induce substantial protection against virulent L. major infection in both genetically susceptible and resistant mice. We investigated the capacity of dhfr-ts- to protect against heterologous infection by L. amazonensis. The degree of protection was evaluated by immunization of BALB/c or C57BL/6 mice with E10-5A3, followed by L. amazonensis challenge. Whether immunized by subcutaneous (SC) or intravenous (IV) inoculation, susceptible and resistant mice displayed a partial degree of protection against challenge with virulent L. amazonensis. SC-immunized BALB/c mice developed lesions 40 to 65% smaller than non immunized mice, while IV immunization led to protection ranging from 40 to 75% in four out of six experiments compared to non immunized animals. The resistant C57BL/6 mice displayed comparable degrees of protection, 57% by SC and 49% by IV immunization. Results are encouraging as it has been previously difficult to obtain protection by SC vaccination against Leishmania, the preferred route for human immunization.     

Induction of multiple chemokine and colony-stimulating factor genes in experimental Burkholderia pseudomallei infection

Melioidosis is a disease of the tropics caused by the facultative intracellular bacterium Burkholderia pseudomallei. In human infection, increased levels of IFN-gamma in addition to the chemokines interferon-gamma-inducible protein 10 (IP-10) and monocyte interferon-gamma-inducible protein (Mig) have been demonstrated. However, the role of these and other chemokines in the pathogenesis of melioidosis remains unknown. Using BALB/c and C57BL/6 mice as models of the acute and chronic forms of human melioidosis, the induction of mRNA was assessed for various chemokines and CSF (G-CSF, M-CSF, GM-CSF, IP-10, Mig, RANTES, MCP-1, KC and MIP-2) in spleen and liver following B. pseudomallei infection. Patterns of chemokine and CSF induction were similar in liver and spleen; however, responses were typically greater in spleen, which reflected higher tissue bacterial loads. In BALB/c mice, high-level expression of mRNA for all chemokines and CSF investigated was demonstrated at day 3 postinfection, correlating with peak bacterial load and extensive infiltration of leucocytes. In contrast, increased mRNA expression and bacterial numbers in C57BL/6 mice were greatest between 4 and 14 days following infection. This paralleled increases in the size and number of abscesses in liver and spleen of C57BL/6 mice at days 3 and 14 postinfection. Earlier induction of cytokine-induced neutrophil chemoattractant (KC), macrophage inflammatory protein-2 (MIP-2), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage CSF (GM-CSF) and macrophage CSF (M-CSF) mRNA was demonstrated in spleen, while MIP-2, MCP-1, IP-10 and Mig were demonstrated in liver of BALB/c mice when compared to spleen and liver of C57BL/6. The magnitude of cellular responses observed in the tissue correlated with increased levels of the chemokines and CSF investigated, as well as bacterial load. Compared with C57BL/6 mice, greater infiltration of neutrophils was observed in liver and spleen of BALB/c mice at day 3. In contrast, early lesions in C57BL/6 mice predominantly comprised macrophages. These results suggest that the inability of BALB/c mice to contain the infection at sites of inflammation may underlie the susceptible phenotype of this mouse strain towards B. pseudomallei infection.     

Systematic Literature Review of Risk Factors and Treatments for Ulcerative Dermatitis in C57BL/6 Mice

Ulcerative dermatitis (UD) in C57BL/6 mice is poorly understood and challenging to treat. We sought to evaluate the evidence regarding commonly cited risk factors for UD and reported UD treatments. The terms ‘ulcerative dermatitis’ and ‘C57BL/6’ were used to search 3 electronic databases. The resulting 347 articles were screened to identify publications that compared the risk of spontaneous UD in wild-type C57BL/6 mice according to sex, season, diet, or age and those that compared the degree of healing or rate of lesion resolution according to the intervention used. Articles were evaluated by using published criteria for assessing methodologic quality, including study design, number of animals per study group, case definition, method of diagnosis, randomization, enrollment criteria, exclusion criteria, and outcomes. The search identified 11 publications on risk factors that met the inclusion criteria, and no publication on UD treatment met all of the criteria. Relaxing the inclusion criteria for reporting of risk factors and treatment outcomes to include both wild-type C57BL/6 mice and genetically engineered mice on a B6 background yielded 12 publications on risk factors and 3 publications on treatment. Dietary factors, particularly caloric restriction, appear to influence UD risk. Female sex was inconsistently associated with a higher risk of UD, which most often occurred in 13- to 24-mo-old mice in the studies that were reviewed. Only 1 of the 3 publications that evaluated UD treatments included an untreated group or alternative therapy control. Further research is needed to explore epidemiologic aspects of UD and to compare treatment options.Abbreviations: B6, C57BL/6; GEM, genetically engineered mouse; UD, ulcerative dermatitisUlcerative dermatitis (UD) is a common condition of several strains of laboratory mice, especially C57BL/6 (B6) mice. The condition is characterized by intense scratching and ulcerative skin lesions of the dorsal cervicothoracic region that are notoriously resistant to treatment.^1,13,16 Large numbers of mice are affected with UD each year, given that B6 mice and genetically engineered mice on a B6 background are some of the most commonly used mice in research.^4,10,16 Although an overall UD prevalence or incidence is unknown for B6 mice, in some reports more than 30% of the mice developed UD during the study period.^1,12 Mice with this disease experience distress related to the severe pruritus and the progressive nature of the lesions.^1,6,12 Concerns regarding animal wellbeing and the potential confounding effects of this disease on research endpoints frequently lead to euthanasia of affected mice.¹⁶ However, despite the devastating effect of this condition in laboratory animal medicine, the pathogenesis of UD is poorly understood and, accordingly, a consistently effective treatment is unavailable.The cause of UD is speculated to be multifactorial.^6,28 The risk of UD reportedly is affected by sex, age, season, and various diets, although not all of these effects have consistently been associated with UD.^13,24,29 For example, female mice have been found to be at increased risk in some studies^13,23 but not in others.^1,16,17 In addition to being clinically useful, identifying reliable risk factors may be advantageous in forming hypotheses regarding the etiology of UD. Therefore, the first aim of this systematic review is to identify peer-reviewed literature that compares the incidence or prevalence of spontaneous UD according to sex, age, season, or diet and to evaluate the scientific evidence for these risk factors.In addition, various treatments for UD have had limited success.^1,8,16,29 As a result, the treatment of UD is largely determined by clinician preference and personal experience. The second aim of this review is to identify studies that report treatments for UD and the quality of evidence supporting the use of the treatment.     

Influence of long-term treatment with pravastatin on the survival, evolution of cutaneous lesion and weight of animals infected by Leishmania amazonensis

The high toxicity of current drugs for treatment of leishmaniasis is a major hindrance for controlling the disease. Pravastatin is a well-known drug with anti-inflammatory and immunomodulatory properties that may modulate host defense mechanisms against Leishmania. We evaluated the influence of prolonged pravastatin treatment on the survival of Leishmania amazonensis-infected animals (BALB/c, C57BL6 mice and Syrian hamsters), including weekly measurement of cutaneous lesions (footpad thickness) and weight. Pravastatin improved survival of Leishmania-infected BALB/c mice but not of infected C57BL6 mice or hamsters. On the 50th week of follow-up, 71% of pravastatin-treated Leishmania-infected BALB/c mice were alive against 29% of control group (p < 0.01). Low footpad thickness was found on BALB/c pravastatin treated mice from the 14th week (p < 0.05), and 20th week onward for C57BL6 treated mice. Pravastatin treatment decreased weight loss in Leishmania-infected C57BL6 mice and Syrian hamsters, but not infected BALB/c mice. Our results points to beneficial effects of pravastatin on the evolution of the disease in the murine leishmaniasis model.