The effect of topical instillation of 2.5% phenylephrine and 1.0% tropicamide on the blood pressure of hypertensive patients

Background: Pupillary dilation is necessary to complete a thorough examination of the internal ocular structures and perform threshold visual fields on the automated perimeter. In our clinic, the topical instillation of 2.5% phenylephrine and 1.0% tropicamide following one drop of topical anesthetic is used routinely for pupil dilation. The vasoconstrictive effects of phenylephrine can cause an increase in peripheral resistance resulting in elevation of systolic and diastolic blood pressures. A rise in systemic blood pressure has been shown to occur following topical instillation of phenylephrine (Heath, Arch Ophthalmol, 1936;16:839–846). This study investigates the effect of topical instillation of 2.5% phenylephrine and 1.0% tropicamide on the blood pressure of known hypertensive patients 30 and 70 min after instillation. Methods: 118 hypertensive patients, all of whom were being treated with anti-hypertensive medications, were involved in the study. Fifty-six patients were dilated with two drops 2.5% phenylephrine and two drops 1.0% tropicamide instilled 5 min apart after one drop of local anesthetic (proparacaine 0.5%). The remaining 62 patients were examined but not dilated. Blood pressure was measured using a sphygmomanometer and stethoscope (right arm sitting) prior to dilation and 30 and 70 min following drop instillation. Results: No clinically significant increase in blood pressure at 30 and 70 min after instillation was observed in the hypertensive group that was dilated. In addition, the change in blood pressure of the dilated group and undilated group was not statistically significant. Conclusion: This study shows that pupillary dilation with 2.5% phenylephrine and 1.0% tropicamide did not significantly increase systemic blood pressure in this population of hypertensive patients.     

Distribution of Mason-Pfizer Virus-Specific Sequences in the DNA of Primates

Iodinated Mason-Pfizer virus (MPV) 60-70S RNA has been used in molecular hybridization experiments to determine the distribution of MPV-specific proviral sequences in the DNAs of primates. Approximately 20% of the MPV genome is present as endogenous provirus in rhesus monkeys. Competitive hybridization experiments showed no homology between MPV 60-70S RNA and the 60-70S RNAs of M7, RD-114, and the simian sarcoma virus. No MPV-specific proviral sequences were detected in the DNAs of apparently normal tissues of various species of New World monkeys, apes, and humans. The part of the MPV genome that is endogenous to rhesus is also endogenous to the other species of Old World monkeys examined: baboon, African green, and patas. This was determined as a result of the following observations: (i) C(0)t(1/2) values and final extent of hybridization were the same for all four species. (ii) T(m) values of MPV 60-70S RNA and DNA of all four species were identical. (iii) The removal of MPV sequences endogenous to rhesus tissues by recycling against rhesus DNA resulted in the loss of any hybridizable MPV RNA to the DNAs of baboon, African green, and patas tissues. (iv) Mixing experiments of rhesus, African green, and baboon DNAs resulted in the same kinetics of hybridization as did rhesus DNA alone, when hybridized with MPV 60-70S RNA. These findings demonstrate that sequences that constitute an integral part of the MPV genome are conserved in the DNAs of several different species of Old World monkeys.     

Neutralizing antibody responses in Africa green monkeys naturally infected with simian immunodeficiency virus (SIVagm)

Abstract: This study assessed the magnitude and cross-reactivity of the neutralizing antibody response generated by natural SIV infection in wild-caught African green monkeys. Neutralizing antibodies of variable potency, sometimes exceeding a titer of 1:1,000, were detected in 20 of 20 SIV-seropositive African green monkeys in Kenya. Detection of those neutralizing antibodies was dependent on the strain of virus and the cells used for assay, where the most sensitive detection was made with SIVagml532 in Sup T1 cells. Potent neutralization of SIVagml532 was seen with contemporaneous autologous serum. Potent neutralization was also detected with laboratory-passaged SIVmac251 and SIVsmB670, but not with SIVsmE660 and two additional strains of SIVagm. Serum samples from rhesus macaques (Macaca mulatta) experimentally infected with either SIVmac251 or SIVsmE660 were capable of low-level neutralization of SIVagm. These results indicate that natural infection with SIV can generate strain-specific neutralizing antibodies in African green monkeys. They also indicate that some neutralization determinants of SIVagm are partially shared with SIV strains that arose in sooty mangabys and were subsequently transmitted to rhesus macaques.     

Mitochondrial Diversity and Distribution of African Green Monkeys (Chlorocebus Gray, 1870)

African green monkeys (Chlorocebus) represent a widely distributed and morphologically diverse primate genus in sub‐Saharan Africa. Little attention has been paid to their genetic diversity and phylogeny. Based on morphological data, six species are currently recognized, but their taxonomy remains disputed. Here, we aim to characterize the mitochondrial (mt) DNA diversity, biogeography and phylogeny of African green monkeys. We analyzed the complete mitochondrial cytochrome b gene of 126 samples using feces from wild individuals and material from zoo and museum specimens with clear geographical provenance, including several type specimens. We found evidence for nine major mtDNA clades that reflect geographic distributions rather than taxa, implying that the mtDNA diversity of African green monkeys does not conform to existing taxonomic classifications. Phylogenetic relationships among clades could not be resolved suggesting a rapid early divergence of lineages. Several discordances between mtDNA and phenotype indicate that hybridization may have occurred in contact zones among species, including the threatened Bale monkey (Chlorocebus djamdjamensis). Our results provide both valuable data on African green monkeys’ genetic diversity and evolution and a basis for further molecular studies on this genus. Am. J. Primatol. 75:350‐360, 2013. © 2013 Wiley Periodicals, Inc.     

Congenital malformations and twinning in a breeding colony of Old World monkeys

Clinical and necropsy records of malformations in Old World monkeys were compiled. The numbers of malformations and birth incidence rate for each species were: Rhesus macaque (Macaca mulatta) 3 (1.02%); Cynomolgus macaque (Macaca fascicularis) 11 (1.62%); Stumptail macaque (Macaca arctoides) 3 (1.55%); African green monkey (Cercopithecus aethiops) 4 (1.5%). There was one pair of rhesus twins (twinning rate: 0.34%). Cardiovascular and central nervous system lesions accounted for 55% of all malformations. Only two of the malformations were in inbred infants. Nine of twenty-one colony-born malformed infants lived 24 hours or more.     

Ophthalmoscopic observations of ocular fundus in colony-born cynomolgus monkeys aged from 0 day to 90 days

Apparently healthy 242 colony-born cynomolgus monkeys (Macaca fascicularis) aged from 0 day to 90 days were examined for the findings of ocular fundus by using ophthalmoscope. One drop of mixed solution of 0.5% tropicamide and 0.5% phenylephrine hydrochloride was instilled into each eye of the monkey. Then, those monkeys were anesthetized with ketamine-HC1 at the dose level of 10mg/kg B. W. Regular and fluorescein photographs were taken with Kowa RC-II ophthalmoscope-camera by using daylight typed color film. Following findings were obtained in each age class: Retinal color was salmon pink with 0 to 3-days-old neonates, salmon pink and blue to green with 7 days to 14-days-old animals and blue to green with 60-days to 90-days-old monkeys. As regards optic disc, 0- to 14-days-old animals were observed to be light orange in color, and the infant aged more than 28-days showed orange color. Retinal arteries and veins were lightly reddish in color with every age class. Macular color was salmon pink in 0-day-old cases, slightly dark in 3-days-old neonates and very dark after 14-days of age. Lightly retinal reflex was noted in 0- and 7-days-old animals. The reflex was observable in 14-days-old animals without any case of exception. Retinal hemorrhages were recorded in 22 (67%) of 36 neonates born in natural condition and 10 (33%) of 30 neonates born by cesarean section. These findings will be useful as the criteria for ophthalmoscopic observations of the cynomolgus monkeys as laboratory use.     

A species comparison of low density lipoprotein heterogeneity in nonhuman primates fed atherogenic diets

Six male cynomolgus monkeys and five male African green monkeys were fed dietary cholesterol to induce hypercholesterolemia. The two groups studied had equivalent total plasma cholesterol concentrations. Low density lipoproteins (LDL) were isolated from whole plasma by ultracentrifugation and separated from other lipoprotein classes by agarose column chromatography. LDL were further subfractionated by density gradient ultracentrifugation in a VTi-50 vertical rotor. The material within five density regions was pooled from each sample and molecular weight, electrophoretic mobility, apoprotein heterogeneity, and percentage composition were determined for each subfraction. In general, cynomolgus monkey LDL were larger and more polydisperse than African green monkey LDL, and the LDL subfractions of cynomolgus monkeys were generally of lower densities although molecular weights at any density were in the same range for both species. ApoB-100 was the major apoprotein in each subfraction. ApoE was frequently present in the less dense subfractions while apoA-I was often seen in the more dense subfractions. Cynomolgus monkey LDL appeared to contain more apoE than African green monkey LDL. Over the entire spectrum of LDL, the percentage composition of the particles at any given density was indistinguishable between the species. In general, the average cynomolgus monkey LDL was larger, more polydisperse, less dense, and appeared to contain more apoE than the average African green monkey LDL. One or all of these differences might help explain the increased susceptibility to diet-induced atherosclerosis seen in cynomolgus monkeys.     

Persistent pupillary membranes in a cynomolgus monkey

Three thousand and five apparently healthy cynomolgus monkeys (Macaca fascicularis) were examined for the finding of the anterior part of the oculi by using an ophthalmoscope. One drop of the mixed solution of 0.5% tropicamide and 0.5% phenylephrine hydrochloride was instilled into each eye of the animal. Then, those monkeys were anesthetized with ketamine-HC1 at the dose level of 10 mg/kg B. W.. One monkey had opaque membranes of tan to brown color, extending from some part of collarette of the iris to the other part of collarette like the network over the pupil. This finding was diagnosed to be bilateral persistent pupillary membranes. Further breeding studies will be carried to determine if this case in hereditary.     

Enzootic simian piroplasm (Entopolypoides macaci ) in wild-caught Kenyan non-human primates

Background Three species of non‐human primates comprising African green monkeys (AGMs), (Cercopithecus aethiops, n = 89), Syke’s monkeys (Cercopithecus mitis, n = 60) and olive baboons (Papio cynocephalus anubis, n = 30), were screened for Entopolypoides macaci. Methods Observation of blood smears prepared from these animals revealed E. macaci infection rate of 42.7% in AGMs, 35% in Syke’s monkeys and 33.3% in baboons. Results Gender infection rate was 38.2% in females and 29% in males. Statistically, there was no significant difference in infection rates between the monkey species and sexes (P > 0.05). Subsequent indirect immuno fluorescent antibody test supported the morphological appearance of E. macaci observed by microscopy. Sera from infected animals reacted positively (1:625) with E. macaci antigen, but not to Babesia bigemina or B. bovis antigen at 1:125 titer. Conclusion This study has revealed high prevalence of E. macaci infection in all three widely distributed Kenyan non‐human primates. With the continued use of these animals as models for human parasitic diseases, the presence of this highly enzootic parasite should be noted.     

The effect of harp music on heart rate, mean blood pressure, respiratory rate, and body temperature in the African green monkey

BACKGROUND: The effectiveness of recorded harp music as a tool for relaxation for non-human primates is explored in this study. METHODS: Konigsberg Instruments Model T27F-1B cardiovascular telemetry devices were implanted into nine African green monkeys (Chlorocebus aethiops). After post-surgical recovery, animals were exposed to recorded harp music. Telemetry data were collected on heart rate, mean blood pressure, respiratory rate, and body temperature for a 30-minute baseline period before music exposure; a 90-minute period of music exposure; and a 90-minute post-exposure period, where no music was played. RESULTS: No statistical differences were noted in heart rate, mean blood pressure, respiratory rate, and body temperature between pre-exposure, exposure, and post-exposure periods. CONCLUSIONS: The lack of response in these African green monkeys may be attributable to their generally calm demeanor in captivity; experiments with a more excitable species such as the rhesus macaque might demonstrate a significant relaxation response to music.     

Serological survey for two simian retroviruses in macaques and African green monkeys

Colonies of nonhuman primates at the Bowman Gray School of Medicine (BGSM) were tested for antibodies to two retroviruses associated with immunodeficiency by indirect immunofluorescence (IFA) and western blot. A total of 471 cynomolgus macaques (Macaca fascicularis), 144 rhesus monkeys (M. mulatta) and 67 stumptail monkey M. arctoides) were tested for SRV-1, and 152 African green monkeys (Cercopithecus aethiops) were tested for SIV. Of the macaques tested, 170 (36%) cynomolgus, 5 (3%) rhesus and 8 (12%) stumptails were positive for SRV-1 antibodies by IFA. Of the African green monkeys, 54 (36%) were IFA positive for SIV antibodies. A total of 143 African green monkeys tested by IFA also were tested by western blot. In the African green monkeys, the IFA had a positive predictive value of 98% and a negative predictive value of 96%. Of 176 IFA positive macaque sera tested by western blot, 49 (28%) were positive, 55 (31%) were considered equivocal (only one band, usually to p27 core protein), and 72 (41%) were negative.     

Aerosol exposure to Zaire ebolavirus in three nonhuman primate species: differences in disease course and clinical pathology

There is little known concerning the disease caused by Zaire ebolavirus (ZEBOV) when inhaled, the likely route of exposure in a biological attack. Cynomolgus macaques, rhesus macaques, and African green monkeys were exposed to aerosolized ZEBOV to determine which species might be the most relevant model of the human disease. A petechial rash was noted on cynomolgus and rhesus macaques after fever onset but not on African green monkeys. Fever duration was shortest in rhesus macaques (62.7 ± 16.3 h) and longest in cynomolgus macaques (82.7 ± 22.3 h) and African green monkeys (88.4 ± 16.7 h). Virus was first detectable in the blood 3 days after challenge; the level of viremia was comparable among all three species. Hematological changes were noted in all three species, including decreases in lymphocyte and platelet counts. Increased blood coagulation times were most pronounced in African green monkeys. Clinical signs and time to death in all three species were comparable to what has been reported previously for each species after parenteral inoculation with ZEBOV. These data will be useful in selection of an animal model for efficacy studies.     

Pulmonary immunoreactive calcitonin in the African green monkey (Cercopithecus aethiops): Anatomic distribution

The hormone calcitonin, which occurs predominantly within the C cells of the mammalian thyroid gland, is also found within the pulmonary endocrine cells of the epithelium of the tracheobronchial tree. A study was made of the distribution of immunoreactive calcitonin (iCT) in the African green monkey. Using two different region-specific antisera, the total respiratory iCT comprised 2.5% and 5.8% of the total thyroid iCT. The mean concentration of iCT in the right lung exceeded that in the left, and the mean concentration of the right middle or right upper lobe exceeded that of all other lobes. Embryologically, the ultimobranchial bodies contribute their iCT-producing C cell primordia to the thyroid gland near the level of the primitive laryngotracheal cleft and shortly after the early arborization of the bronchial tree. In monkeys and most other mammals, the right main stem bronchus is larger and develops earlier than the left. The data suggest an early migration of cells from the ultimobranchial bodies to the bronchi, eventually giving rise to the iCT-containing pulmonary endocrine cells.     

Distinct severe acute respiratory syndrome coronavirus-induced acute lung injury pathways in two different nonhuman primate species

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), caused by influenza A virus H5N1 and severe acute respiratory syndrome coronavirus (SARS-CoV), supposedly depend on activation of the oxidative-stress machinery that is coupled with innate immunity, resulting in a strong proinflammatory host response. Inflammatory cytokines, such as interleukin 1β (IL-1β), IL-8, and IL-6, play a major role in mediating and amplifying ALI/ARDS by stimulating chemotaxis and activation of neutrophils. To obtain further insight into the pathogenesis of SARS-CoV-associated ALI, we compared SARS-CoV infections in two different nonhuman primate species, cynomolgus macaques and African green monkeys. Viral titers in the upper and lower respiratory tract were not significantly different in SARS-CoV-infected macaques and African green monkeys. Inflammatory cytokines that play a major role in mediating and amplifying ALI/ARDS or have neutrophil chemoattractant activity, such as IL-6, IL-8, CXCL1, and CXCL2, were, however, induced only in macaques. In contrast, other proinflammatory cytokines and chemokines, including osteopontin and CCL3, were upregulated in the lungs of African green monkeys to a significantly greater extent than in macaques. Because African green monkeys developed more severe ALI than macaques, with hyaline membrane formation, some of these differentially expressed proinflammatory genes may be critically involved in development of the observed pathological changes. Induction of distinct proinflammatory genes after SARS-CoV infection in different nonhuman primate species needs to be taken into account when analyzing outcomes of intervention strategies in these species.     

Simian immunodeficiency viruses from African green monkeys display unusual genetic diversity.

African green monkeys are asymptomatic carriers of simian immunodeficiency viruses (SIV), commonly called SIVagm. As many as 50% of African green monkeys in the wild may be SIV seropositive. This high seroprevalence rate and the potential for genetic variation of lentiviruses suggested to us that African green monkeys may harbor widely differing genotypes of SIVagm. To investigate this hypothesis, we determined the entire nucleotide sequence of an infectious proviral molecular clone of SIVagm (155-4) and partial sequences (long terminal repeat and Gag) of three other distinct SIVagm isolates (90, gri-1, and ver-1). Comparisons among the SIVagm isolates revealed extreme diversity at the nucleotide and amino acid levels. Long terminal repeat nucleotide sequences varied up to 35% and Gag protein sequences varied up to 30%. The variability among SIVagm isolates exceeded the variability among any other group of primate lentiviruses. Our data suggest that SIVagm has been in the African green monkey population for a long time and may be the oldest primate lentivirus group in existence.     

Simian Immunodeficiency Virus (SIV) from Sun-Tailed Monkeys (Cercopithecus solatus): Evidence for Host-Dependent Evolution of SIV within the C. lhoesti Superspecies

Recently we reported the characterization of simian immunodeficiency virus (SIVlhoest) from a central African l'hoest monkey (Cercopithecus lhoesti lhoesti) that revealed a distant relationship to SIV isolated from a mandrill (SIVmnd). The present report describes a novel SIV (SIVsun) isolated from a healthy, wild-caught sun-tailed monkey (Cercopithecus lhoesti solatus), another member of the l'hoest superspecies. SIVsun replicated in a variety of human T-cell lines and in peripheral blood mononuclear cells of macaques (Macaca spp.) and patas monkeys (Erythrocebus patas). A full-length infectious clone of SIVsun was derived, and genetic analysis revealed that SIVsun was most closely related to SIVlhoest, with an amino acid identity of 71% in Gag, 73% in Pol, and 67% in Env. This degree of similarity is reminiscent of that observed between SIVagm isolates from vervet, grivet, and tantalus species of African green monkeys. The close relationship between SIVsun and SIVlhoest, despite their geographically distinct habitats, is consistent with evolution from a common ancestor, providing further evidence for the ancient nature of the primate lentivirus family. In addition, this observation leads us to suggest that the SIVmnd lineage should be designated the SIVlhoest lineage.     

Comparative normal levels of serum triiodothyronine and thyroxine in nonhuman primates.

Normative values were obtained for triiodothyronine and thyroxine from four species of Old World primate (chimpanzees, rhesus monkeys, African green monkeys and talopoin monkeys) and a single species of New World primate (squirrel monkeys) represented by two subspecies, Colombian and Bolivian. The Bolivian squirrel monkeys exhibited the lowest values for both triiodothyronine and thyroxine. Male talapoins had the highest levels of thyroxine. Significant differences were found in levels of triiodothyronine and thyroxine between males and females of the same species and between the two subspecies of squirrel monkeys. Triiodothyronine:thryroxine ratios were consistently lower in the males of all species examined.     

Salt stress enhanced antioxidant response in callus of three halophytes (Salsola baryosma, Trianthema triquetra, Zygophyllum simplex) of Thar Desert

Effects of salinity on growth, protein content, proline, catalase and antioxidant enzyme activity in callus of three halophytes of the Thar Desert; Salsola baryosma, Trianthema triquetra and Zygophyllum simplex were evaluated. Callus tissues were cultured on Murashige and Skoog’s medium containing different concentrations of NaCl (50, 100 and 200 mM). Increase in dry weight and soluble proteins were observed in the callus exposed to lower salinity (50 and 100 mM NaCl) in all the three species, whereas on the medium containing 200 mM NaCl, significant decrease in these two growth parameters was recorded. Under the salinity stress maximum proline accumulation was found in S. baryosma with parallel increase in soluble sugars. Among the three species, T. triquetra callus showed maximum CAT activity with 50 and 100 mM NaCl treatment, whereas the enzyme activity decreased at 200 mM NaCl treatment in all three species. The antioxidant potential steadily elevated under salt treatment in all the above three species using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant potential (FRAP) assay. Whereas, superoxide dismutase (SOD) quenching were recorded maximum at low (50 and 100 mM) concentrations in all the three species. However, T. triquetra callus showed maximum total phenolic content (TPC) 15 mg GAE g^?1 with the elevated concentration of NaCl up to 200 mM, and S. baryosma callus showed lower TPC as compared to both species. A significant correlation between antioxidant capacity and TPC was observed indicating that phenolic compounds are the major contributors to the antioxidant potential in these halophyte species. FRAP and DPPH activity of Z. simplex showed maximum correlation (R = 0.992), as compared to other two species. We can conclude that all the three species exhibit a protection mechanism by sustaining growth parameters and antioxidant capacity. Due to high antioxidant property of all these species, the plant extracts may be included in nutraceutical formulations.     

Increased inherent intestinal granzyme B expression may be associated with SIV pathogenesis in Asian non-human primates

Background Unlike Asian non‐human primates, chronically SIV‐infected African non‐human primates (NHP) display a non‐pathogenic disease course. The different outcomes may be related to the development of an SIV‐mediated breach of the intestinal mucosa in the Asian species that is absent in the African animals. Methods To examine possible mechanisms that could lead to the gut breach, we determined whether the colonic lamina propria (LP) of SIV‐naïve Asian monkeys contained more granzyme B (GrB) producing CD4 T cells than did that of the African species. GrB is a serine protease that may disrupt mucosal integrity by damaging tight junction proteins. Results We found that the colonic LP of Asian NHP contain more CD4⁺/GrB⁺ cells than African NHP. We also observed reduced CD4 expression on LP T cells in African green monkeys. Conclusion Both phenotypic differences could protect against SIV‐mediated damage to the intestinal mucosa and could lead to future therapies in HIV⁺ humans.     

Characterization and comparison of testicular LH/hCG receptors of rhesus monkeys (Macaca mulatta) and green monkeys (Cercopithecus aethiops)

Testicular luteinizing hormone (LH/hCG) receptors were characterized in seven green monkeys and compared with those of four rhesus monkeys. Testicular tissue showed high binding affinity for ¹²⁵I-hCG, (0.9–2.5 × 10⁹ M^?1, and 0.7–1.64 × 10⁹ M^?1 respectively, for green and rhesus monkeys) and low binding capacity (0.343–0.682 fmol/mg and 0.198–0.355 fmol/mg testicular homogenate, respectively). There was no difference in binding affinity between the two groups. Testicular LH/hCG receptors in both species bound human LH (hLH) and hCG but did not cross react with ovine LH (oLH). Rat testicular tissue showed similar high binding affinity (6.4 × 10⁹ M^?1) and low binding capacity (1.04 fmol/mg tissue homogenate) for ¹²⁵I-hCG. Rat LH/hCG receptors bound hLH, hCG, and oLH to a similar degree.