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Milton H Stetson - One of the best experts on this subject based on the ideXlab platform.

  • food availability and photoperiod affect reproductive development and maintenance in the marsh rice rat Oryzomys palustris
    Physiology & Behavior, 2003
    Co-Authors: Kent E Edmonds, Leah Riggs, Milton H Stetson
    Abstract:

    To examine whether photoperiod and food availability interact to influence reproductive development (Experiment 1), we exposed juvenile male and female rice rats to 16L:8D or 14L:10D and to ad lib, 80% of ad lib, or 60% of ad lib food intake from 3 to 8 weeks of age and recorded body and reproductive organ masses. Absolute paired testis masses were similar in ad lib and 80% of ad lib groups but significantly different than the 60% of ad lib group in both photoperiods. Relative paired testis masses were significantly different in the 80% and 60% of ad lib groups on 16L:8D only. Absolute seminal vesicle masses (SVM) were directly dependent upon the level of food restriction in both photoperiods, but relative SVMs were different only in the 60% of ad lib group. Terminal body masses were also directly dependent upon the level of food restriction and were greater on 16L:8D than on 14L:10D at most levels of food availability. In juvenile females, absolute uterine mass was only affected in the 60% of ad lib group on 14L:10D, while absolute paired ovary masses were affected on both photoperiods in the 60% of ad lib groups only. There was no effect of photoperiod or food on relative uterine and paired ovary masses. Terminal body mass was affected by food intake in both photoperiods. Lastly, in adult males (Experiment 2), photoperiod and food restriction affected reproductive function. Within a photoperiod, there was no effect of food restriction (75% of ad lib) on the testes, seminal vesicles, or testosterone levels in animals housed on 16L:8D, but terminal body mass was significantly reduced. On 12L:12D, however, food restriction significantly decreased testes and SVMs relative to ad lib-fed controls. Testosterone levels were reduced regardless of food availability. There was no effect of food restriction on terminal body mass. These results suggest that multiple potential environmental cues can be utilized to affect gonadal status in both juvenile and adult marsh rice rats.

  • Effects of age and photoperiod on reproduction and the spleen in the marsh rice rat (Oryzomys palustris)
    American journal of physiology. Regulatory integrative and comparative physiology, 2001
    Co-Authors: Kent E Edmonds, Milton H Stetson
    Abstract:

    To examine the interactions between age and photoperiod on reproduction and spleen weights, we exposed adult male and female rice rats of various ages to photoperiods of 16:8-h light-dark photoperiods (16L:8D) or 12L:12D. After 10 wk, animals were killed and the following data were recorded: weights of testes, seminal vesicles, uterus, ovaries, body, and spleen and, in addition, vaginal patency. Young adult males displayed a greater degree of testicular and seminal vesicle regression in short photoperiods than did older males; the testes of most older males did not regress in response to short photoperiods. Spleen weight was unresponsive to short photoperiods in all males, but was affected by age. Females, however, exhibited reproductive organ regression and decreased vaginal patency in response to short photoperiods at all ages examined. Body weights were affected by photoperiod in young females, and, as in males, photoperiod had no effect on spleen weights. These data suggest that the reproductive response to photoperiod in adult male rice rats declines with age, whereas in adult females it does not.

  • pineal gland and melatonin affect testicular status in the adult marsh rice rat Oryzomys palustris
    General and Comparative Endocrinology, 1995
    Co-Authors: Kent E Edmonds, Milton H Stetson
    Abstract:

    The effects of the presence or absence of the pineal gland and of melatonin administration were examined on testicular maintenance, regression, and recrudescence in adult male rice rats. Pinealectomy at the beginning of the study caused significant testicular regression in animals housed on both long (16L:8D) and short (12L:12D) photoperiods (Experiment 1). Sham-operated males maintained testicular weight on 16L:8D and underwent testicular regression on 12L:12D. The magnitude of testicular regression in pinealectomized animals was reduced relative to that of sham-operated animals housed on a short photoperiod and occurred on a different time course. Animals pinealectomized after testicular regression had occurred on 12L:12D demonstrated delayed photostimulated testicular recrudescence when housed on 16L:8D, while spontaneous testicular recrudescence was unaffected in animals maintained on 12L:12D (Experiment 2). Administration of melatonin via subcutaneous implants at the beginning of the study (Experiment 3) produced similar effects on testicular function attributed to pinealectomy in Experiment 1. Finally, melatonin implants administered after the testes regressed on 12L:12D delayed both photostimulated and spontaneous testicular recrudescence in animals housed on long or short photoperiods, respectively (Experiment 4). These results suggest a role for both the pineal gland and melatonin at various stages of the annual reproductive cycle of the male rice rat.

  • effects of prenatal and postnatal photoperiods and of the pineal gland on early testicular development in the marsh rice rat Oryzomys palustris
    Biology of Reproduction, 1995
    Co-Authors: Kent E Edmonds, Milton H Stetson
    Abstract:

    Prepubertal male rice rats are responsive reproductively to photoperiod early in postnatal development. Testicular growth was inhibited in animals gestated and reared to 28 days of age on photoperiods ranging from 8 to 13 h of light per day, and stimulated in animals reared on 14 h or more of light per day, suggesting a critical photoperiod between 13 and 14 h for testicular growth. In addition, postnatal photoperiod markedly affected testicular development in animals exposed to various prenatal and postnatal photoperiods. Postnatal exposure to constant light unmasked effects of the prenatal photoperiod on testicular development. Exposure of rice rats to short or long photoperiods during the period of lactation (Days 1-14 of life) affected testicular maturation. In addition, alteration of the photoperiod experienced after Day 14 of life (post-lactational) markedly affected testicular development and was the primary factor determining whether maturation would occur. Finally, pinealectomy had little to no effect on the magnitude of testicular development in animals maintained on the presurgical photoperiod, but did prevent animals from demonstrating the appropriate testicular response to a new photoperiod after surgery. These data suggest that early testicular development in rice rats is affected by the prenatal and postnatal photoperiod and that the pineal gland is involved in the transduction of this environmental information.

  • effects of photoperiod on pineal melatonin in the marsh rice rat Oryzomys palustris
    Journal of Pineal Research, 1995
    Co-Authors: Kent E Edmonds, Mark D Rollag, Milton H Stetson
    Abstract:

    Pineal melatonin content was examined under four different photoperiods (10L:14D, 12L:12D, 14L:10D, and 16L:8D) in adult female rice rats (Experiment 1). Pineal melatonin was basal during the light and increased beginning 1 hr after lights off. Within 2 hr after lights off, melatonin increased to levels that were maintained throughout the dark period. In all but one photoperiod (10L:14D), melatonin remained elevated prior to light onset and decreased markedly within one hour after lights on. In addition, the duration of pineal melatonin was inversely related to the length of the photoperiod. In Experiment 2, the time course of pineal melatonin content on 16L:8D was examined every 20 min during the first hour after lights off and the first hour after lights on. Melatonin content increased gradually during the first hour and decreased markedly within 20 min after lights on. These data show that pineal melatonin in female rice rats is regulated by photoperiod.

Kent E Edmonds - One of the best experts on this subject based on the ideXlab platform.

  • food availability and photoperiod affect reproductive development and maintenance in the marsh rice rat Oryzomys palustris
    Physiology & Behavior, 2003
    Co-Authors: Kent E Edmonds, Leah Riggs, Milton H Stetson
    Abstract:

    To examine whether photoperiod and food availability interact to influence reproductive development (Experiment 1), we exposed juvenile male and female rice rats to 16L:8D or 14L:10D and to ad lib, 80% of ad lib, or 60% of ad lib food intake from 3 to 8 weeks of age and recorded body and reproductive organ masses. Absolute paired testis masses were similar in ad lib and 80% of ad lib groups but significantly different than the 60% of ad lib group in both photoperiods. Relative paired testis masses were significantly different in the 80% and 60% of ad lib groups on 16L:8D only. Absolute seminal vesicle masses (SVM) were directly dependent upon the level of food restriction in both photoperiods, but relative SVMs were different only in the 60% of ad lib group. Terminal body masses were also directly dependent upon the level of food restriction and were greater on 16L:8D than on 14L:10D at most levels of food availability. In juvenile females, absolute uterine mass was only affected in the 60% of ad lib group on 14L:10D, while absolute paired ovary masses were affected on both photoperiods in the 60% of ad lib groups only. There was no effect of photoperiod or food on relative uterine and paired ovary masses. Terminal body mass was affected by food intake in both photoperiods. Lastly, in adult males (Experiment 2), photoperiod and food restriction affected reproductive function. Within a photoperiod, there was no effect of food restriction (75% of ad lib) on the testes, seminal vesicles, or testosterone levels in animals housed on 16L:8D, but terminal body mass was significantly reduced. On 12L:12D, however, food restriction significantly decreased testes and SVMs relative to ad lib-fed controls. Testosterone levels were reduced regardless of food availability. There was no effect of food restriction on terminal body mass. These results suggest that multiple potential environmental cues can be utilized to affect gonadal status in both juvenile and adult marsh rice rats.

  • Effects of age and photoperiod on reproduction and the spleen in the marsh rice rat (Oryzomys palustris)
    American journal of physiology. Regulatory integrative and comparative physiology, 2001
    Co-Authors: Kent E Edmonds, Milton H Stetson
    Abstract:

    To examine the interactions between age and photoperiod on reproduction and spleen weights, we exposed adult male and female rice rats of various ages to photoperiods of 16:8-h light-dark photoperiods (16L:8D) or 12L:12D. After 10 wk, animals were killed and the following data were recorded: weights of testes, seminal vesicles, uterus, ovaries, body, and spleen and, in addition, vaginal patency. Young adult males displayed a greater degree of testicular and seminal vesicle regression in short photoperiods than did older males; the testes of most older males did not regress in response to short photoperiods. Spleen weight was unresponsive to short photoperiods in all males, but was affected by age. Females, however, exhibited reproductive organ regression and decreased vaginal patency in response to short photoperiods at all ages examined. Body weights were affected by photoperiod in young females, and, as in males, photoperiod had no effect on spleen weights. These data suggest that the reproductive response to photoperiod in adult male rice rats declines with age, whereas in adult females it does not.

  • pineal gland and melatonin affect testicular status in the adult marsh rice rat Oryzomys palustris
    General and Comparative Endocrinology, 1995
    Co-Authors: Kent E Edmonds, Milton H Stetson
    Abstract:

    The effects of the presence or absence of the pineal gland and of melatonin administration were examined on testicular maintenance, regression, and recrudescence in adult male rice rats. Pinealectomy at the beginning of the study caused significant testicular regression in animals housed on both long (16L:8D) and short (12L:12D) photoperiods (Experiment 1). Sham-operated males maintained testicular weight on 16L:8D and underwent testicular regression on 12L:12D. The magnitude of testicular regression in pinealectomized animals was reduced relative to that of sham-operated animals housed on a short photoperiod and occurred on a different time course. Animals pinealectomized after testicular regression had occurred on 12L:12D demonstrated delayed photostimulated testicular recrudescence when housed on 16L:8D, while spontaneous testicular recrudescence was unaffected in animals maintained on 12L:12D (Experiment 2). Administration of melatonin via subcutaneous implants at the beginning of the study (Experiment 3) produced similar effects on testicular function attributed to pinealectomy in Experiment 1. Finally, melatonin implants administered after the testes regressed on 12L:12D delayed both photostimulated and spontaneous testicular recrudescence in animals housed on long or short photoperiods, respectively (Experiment 4). These results suggest a role for both the pineal gland and melatonin at various stages of the annual reproductive cycle of the male rice rat.

  • effects of prenatal and postnatal photoperiods and of the pineal gland on early testicular development in the marsh rice rat Oryzomys palustris
    Biology of Reproduction, 1995
    Co-Authors: Kent E Edmonds, Milton H Stetson
    Abstract:

    Prepubertal male rice rats are responsive reproductively to photoperiod early in postnatal development. Testicular growth was inhibited in animals gestated and reared to 28 days of age on photoperiods ranging from 8 to 13 h of light per day, and stimulated in animals reared on 14 h or more of light per day, suggesting a critical photoperiod between 13 and 14 h for testicular growth. In addition, postnatal photoperiod markedly affected testicular development in animals exposed to various prenatal and postnatal photoperiods. Postnatal exposure to constant light unmasked effects of the prenatal photoperiod on testicular development. Exposure of rice rats to short or long photoperiods during the period of lactation (Days 1-14 of life) affected testicular maturation. In addition, alteration of the photoperiod experienced after Day 14 of life (post-lactational) markedly affected testicular development and was the primary factor determining whether maturation would occur. Finally, pinealectomy had little to no effect on the magnitude of testicular development in animals maintained on the presurgical photoperiod, but did prevent animals from demonstrating the appropriate testicular response to a new photoperiod after surgery. These data suggest that early testicular development in rice rats is affected by the prenatal and postnatal photoperiod and that the pineal gland is involved in the transduction of this environmental information.

  • effects of photoperiod on pineal melatonin in the marsh rice rat Oryzomys palustris
    Journal of Pineal Research, 1995
    Co-Authors: Kent E Edmonds, Mark D Rollag, Milton H Stetson
    Abstract:

    Pineal melatonin content was examined under four different photoperiods (10L:14D, 12L:12D, 14L:10D, and 16L:8D) in adult female rice rats (Experiment 1). Pineal melatonin was basal during the light and increased beginning 1 hr after lights off. Within 2 hr after lights off, melatonin increased to levels that were maintained throughout the dark period. In all but one photoperiod (10L:14D), melatonin remained elevated prior to light onset and decreased markedly within one hour after lights on. In addition, the duration of pineal melatonin was inversely related to the length of the photoperiod. In Experiment 2, the time course of pineal melatonin content on 16L:8D was examined every 20 min during the first hour after lights off and the first hour after lights on. Melatonin content increased gradually during the first hour and decreased markedly within 20 min after lights on. These data show that pineal melatonin in female rice rats is regulated by photoperiod.

Charles F Fulhorst - One of the best experts on this subject based on the ideXlab platform.

  • catacamas virus a hantaviral species naturally associated with Oryzomys couesi coues Oryzomys in honduras
    American Journal of Tropical Medicine and Hygiene, 2006
    Co-Authors: Mary Louise Milazzo, Maria N B Cajimat, Delton J Hanson, Robert D Bradley, Miguel Quintana, Catalina Sherman, Reina Teresa Velasquez, Charles F Fulhorst
    Abstract:

    The primary objective of this study was to extend our knowledge of the geographical distribution, genetic diversity, and natural host associations of the hantaviruses indigenous to North America. Antibody to a hantavirus was found in 5 (20.8%) of 24 Coues' Oryzomys (Oryzomys couesi) and none of 41 other rodents captured near the town of Catacamas in eastern Honduras, and a hantavirus was isolated from one of the antibody-positive Coues' Oryzomys. Analyses of nucleotide and amino acid sequence data indicated that the viral isolate is a strain of a novel hantaviral species (proposed species name "Catacamas virus") that is phylogenetically most closely related to Bayou virus, a hantaviral species that is principally associated with Oryzomys palustris (marsh Oryzomys) in the southeastern United States. Catacamas virus is the first evidence for the occurrence of a hantaviral species in Honduras and the first evidence that a hantaviral species is naturally associated with an Oryzomys species other than O. palustris.

Mary Louise Milazzo - One of the best experts on this subject based on the ideXlab platform.

  • CATACAMAS VIRUS, A HANTAVIRAL SPECIES NATURALLY ASSOCIATED WITH Oryzomys COUESI (COUES ’ Oryzomys) IN HONDURAS
    2015
    Co-Authors: Mary Louise Milazzo, Maria N B Cajimat, Delton J Hanson, Robert D Bradley, Miguel Quintana, Catalina Sherman, Reina T. Velásquez, F. Fulhorst
    Abstract:

    Abstract. The primary objective of this study was to extend our knowledge of the geographical distribution, genetic diversity, and natural host associations of the hantaviruses indigenous to North America. Antibody to a hantavirus was found in 5 (20.8%) of 24 Coues ’ Oryzomys (Oryzomys couesi) and none of 41 other rodents captured near the town of Catacamas in eastern Honduras, and a hantavirus was isolated from one of the antibody-positive Coues ’ Oryzomys. Analyses of nucleotide and amino acid sequence data indicated that the viral isolate is a strain of a novel hantaviral species (proposed species name “Catacamas virus”) that is phylogenetically most closely related to Bayou virus, a hantaviral species that is principally associated with Oryzomys palustris (marsh Oryzomys) in the southeastern United States. Catacamas virus is the first evidence for the occurrence of a hantaviral species in Honduras and the first evidence that a hantaviral species is naturally associated with an Oryzomys species other than O. palustris

  • catacamas virus a hantaviral species naturally associated with Oryzomys couesi coues Oryzomys in honduras
    American Journal of Tropical Medicine and Hygiene, 2006
    Co-Authors: Mary Louise Milazzo, Maria N B Cajimat, Delton J Hanson, Robert D Bradley, Miguel Quintana, Catalina Sherman, Reina Teresa Velasquez, Charles F Fulhorst
    Abstract:

    The primary objective of this study was to extend our knowledge of the geographical distribution, genetic diversity, and natural host associations of the hantaviruses indigenous to North America. Antibody to a hantavirus was found in 5 (20.8%) of 24 Coues' Oryzomys (Oryzomys couesi) and none of 41 other rodents captured near the town of Catacamas in eastern Honduras, and a hantavirus was isolated from one of the antibody-positive Coues' Oryzomys. Analyses of nucleotide and amino acid sequence data indicated that the viral isolate is a strain of a novel hantaviral species (proposed species name "Catacamas virus") that is phylogenetically most closely related to Bayou virus, a hantaviral species that is principally associated with Oryzomys palustris (marsh Oryzomys) in the southeastern United States. Catacamas virus is the first evidence for the occurrence of a hantaviral species in Honduras and the first evidence that a hantaviral species is naturally associated with an Oryzomys species other than O. palustris.

Ignacio J Aguirre - One of the best experts on this subject based on the ideXlab platform.

  • attenuated amiloride sensitive current and augmented calcium activated chloride current in marsh rice rat Oryzomys palustris airways
    iScience, 2019
    Co-Authors: Shinping Kuan, Ignacio J Aguirre, Jonathan G. Messer, Yanshin J Liao, Katelyn M Davis, Jasenka Zubcevic, Leah R Reznikov
    Abstract:

    Prolonged heat and sea salt aerosols pose a challenge for the mammalian airway, placing the protective airway surface liquid (ASL) at risk for desiccation. Thus, mammals inhabiting salt marshes might have acquired adaptations for ASL regulation. We studied the airways of the rice rat, a rodent that inhabits salt marshes. We discovered negligible Na+ transport through the epithelial sodium channel (ENaC). In contrast, carbachol induced a large Cl- secretory current that was blocked by the calcium-activated chloride channel (CaCC) inhibitor CaCCinhi-A01. Decreased mRNA expression of α, β, and γ ENaC, and increased mRNA expression of the CaCC transmembrane member 16A, distinguished the rice rat airway. Rice rat airway cultures also secreted fluid in response to carbachol and displayed an exaggerated expansion of the ASL volume when challenged with 3.5% NaCl. These data suggest that the rice rat airway might possess unique ion transport adaptations to facilitate survival in the salt marsh environment.

  • attenuated amiloride sensitive current and augmented calcium activated chloride current in marsh rice rat Oryzomys palustris airways
    bioRxiv, 2019
    Co-Authors: Shinping Kuan, Ignacio J Aguirre, Jonathan G. Messer, Yanshin J Liao, Katelyn M Davis, Jasenka Zubcevic, Leah R Reznikov
    Abstract:

    Prolonged heat and sea salt aerosols pose a challenge for the mammalian airway, placing the protective airway surface liquid (ASL) at risk for desiccation. Thus, mammals inhabiting salt marshes might have acquired adaptations for ASL regulation. We studied the airways of the rice rat, a rodent that inhabits salt marshes. We discovered negligible Na+ transport through the epithelial sodium channel (ENaC). In contrast, carbachol induced a large Cl- secretory current that was blocked by the calcium-activated chloride channel (CaCC) inhibitor CaCCinh-A01. Decreased mRNA expression of , {beta}, and {gamma} ENaC, and increased mRNA expression of the CaCC transmembrane member 16A distinguished the rice rat airway. Rice rat airway cultures also secreted fluid in response to carbachol and displayed an exaggerated expansion of the ASL volume when challenged with 3.5% NaCl. These data suggest that the rice rat airway might possess unique ion transport adaptations to facilitate survival in the salt marsh environment.

  • cutaneous epitheliotropic t cell lymphoma in a marsh rice rat Oryzomys palustris
    Comparative Medicine, 2015
    Co-Authors: Bryan F Taylor, Christine M Bekkevold, Ignacio J Aguirre, Karl Andrutis, Mary K Reinhard
    Abstract:

    Published reports of spontaneous neoplasia in marsh rice rats (Oryzomys palustris) are sparse. We report here a case of cutaneous epitheliotropic T-cell lymphoma in a 14-mo-old marsh rice rat that involved the ear pinnae, with dissemination to the liver and spleen. Histologically, the thickened ear pinnae showed diffuse infiltration of neoplastic lymphocytes into the epidermis, dermis, and adnexal skin structures, with Pautrier microaggregations present in the epidermis. In addition, neoplastic lymphocytes were observed infiltrating and disrupting the architecture of the liver and spleen. Neoplastic lymphocytes were strongly positive for the T-cell marker CD3 but were negative for the B-cell markers CD19 and CD20. These histologic and immunohistochemical features are consistent with an epitheliotropic T-cell lymphoma, as previously reported in other species, including humans. To our knowledge, this report represents the first published case of spontaneous cutaneous epitheliotropic T-cell lymphoma in a marsh rice rat.

  • breeding husbandry veterinary care and hematology of marsh rice rats Oryzomys palustris a small animal model for periodontitis
    Journal of The American Association for Laboratory Animal Science, 2015
    Co-Authors: Ignacio J Aguirre, Mary K Reinhard, Kent Edmonds, Bernadette Zamora, Jennifer E Pingel, Linda C Thomas, Denisse Cancel, Laura Schneider, August H Battles, Mohammed P Akhter
    Abstract:

    Rice rats (Oryzomys palustris) are a recognized animal model for studying periodontal disease and the photoperiodic regulation of reproduction. Here we share information regarding the breeding, husbandry, veterinary care, and hematologic findings about this animal species to facilitate its use in studies at other research institutions. Rice rats initially were quarantined and monitored for excluded pathogens by using microbiologic, parasitologic, and serologic methods with adult female Mus musculus and Rattus norvegicus sentinel animals. Breeders were paired in a monogamous, continuous-breeding system. Rats were housed in static filter-top cages, maintained on commercial chow under 14:10-h light:dark cycles at 68 to 79 °F (20.0 to 26.1 °C) and 30% to 70% humidity. Rice rats apparently adapt relatively well to standard laboratory conditions, despite their aggressive behavior toward conspecifics and humans. Our analysis of 97 litters revealed that dams gave birth to an average of 5.2 pups per dam and weaned 4.2 pups per dam. Several procedures and biologic reagents normally used in standard laboratory rodents (mice and rats) can be used with rice rats. In addition, we present hematologic and serum chemistry values that can be used as preliminary reference values for future studies involving rice rats.

  • oncologic doses of zoledronic acid induce osteonecrosis of the jaw like lesions in rice rats Oryzomys palustris with periodontitis
    Journal of Bone and Mineral Research, 2012
    Co-Authors: Ignacio J Aguirre, Donald B. Kimmel, Jennifer E Pingel, Alyssa A Williams, Marda Jorgensen, M P Akhter, Lakshmyya Kesavalu, T J Wronski
    Abstract:

    Though osteonecrosis of the jaw (ONJ) is temporally-associated with the use of nitrogen-containing bisphosphonates (N-BPs), a cause-and-effect relationship has not yet been established. We hypothesize that ONJ is a two-stage process in which: (1) risk factors initiate pathologic processes in the oral cavity that lead to a supranormal rate of hard tissue necrosis; and (2) powerful antiresorptives reduce the rate of removal of necrotic bone sufficiently to allow its net accumulation in the jaw. To test this hypothesis, we used the rice rat model of periodontitis. At age 28 days, rats (n = 15/group) were placed on a high-sucrose and casein diet to exacerbate the development of periodontitis. Animals were injected subcutaneously (SC) biweekly with vehicle or alendronate (ALN, 15 µg/kg), or IV once monthly with vehicle, a low dose (LD) of zoledronic acid (ZOL), or a high dose (HD) of ZOL and sacrificed after 6, 12, 18, and 24 weeks. Mandibles and maxillae were analyzed to determine the effects on the: (1) progression of periodontitis; (2) integrity of alveolar bone; (3) status of bone resorption and formation; (4) vascularity; and (5) osteocyte viability. We found that only HD-ZOL induced ONJ-like lesions in mandibles of rice rats after 18 and 24 weeks of treatment. These lesions were characterized by areas of exposed necrotic alveolar bone, osteolysis, a honeycomb-like appearance of the alveolar bone, presence of bacterial colonies, and periodontal tissue destruction. In addition, inhibition of bone formation, a paradoxical abolition of the antiresorptive effect of only HD-ZOL, increased osteocyte necrosis/apoptosis, and decreased blood vessel number were found after 18 and/or 24 weeks. Our study suggests that only HD-ZOL exacerbates the inflammatory response and periodontal tissue damage in rice rats, inducing bone lesions that resemble ONJ. © 2012 American Society for Bone and Mineral Research.