scholarly journals STUDIES UPON THE ETIOLOGY OF DENGUE FEVER

1924 ◽  
Vol 40 (6) ◽  
pp. 835-844 ◽  
Author(s):  
Charles W. Duval ◽  
William H. Harris

We have described the cultivation of a minute organism, upon the special media devised by Noguchi for growing spirochetal organisms, that gives rise to pyrexial and leucocytic reactions in the guinea pig. The reaction in the animal following the injection of culture filtrate is identical with that induced by the inoculation of human dengue blood. While it is possible, it is hardly probable that the infection of animals with cultures of this microorganism several generations removed from the original is due to a mechanically transferred virus with which the visible microorganism cultivated became accidentally associated. Furthermore, it is unlikely that such a virus would remain viable and be carried over to subcultures in sufficient numbers to infect the animal. The microorganisms appear in culture as globoid bodies measuring from 0.1 to 0.3µ in diameter and are arranged singly, in pairs, and in short chains. They readily pass through the Berkefeld filter (N and V) and the filtrate gives rise to a characteristic reaction in the inoculated guinea pig. The filtrate yields in subplants the same globoid bodies of the original culture. Initial cultures have been obtained directly from the blood of the human case as well as from the blood of guinea pigs reacting to the human material. However, only early generations retain the degree of virulence necessary to cause the experimental reaction, the culture of remote generation failing to infect. As far as known this minute organism has characters in common with the globoid bodies of Flexner and Noguchi obtained from cases of poliomyelitis. In plasma semisolid medium the striking feature indicative of growth is colonization, which in itself serves to differentiate the opalescence of the medium occasioned by disintegration of the contained tissue. As regards the presence of spirochetal organisms in the blood of dengue fever, we may state that examination was made of the material from human cases and from. a large number of inoculated animals. Despite the most careful search with the dark-field microscope and repeated examinations of blood specimens stained by the best methods, we have been unable to find any demonstrable spiral organism in the blood of dengue patients or in the experimentally inoculated animal. The minute organism herein described is frequently present in cultures of the blood of human dengue and of animals inoculated with dengue material. The inoculation of the culture into guinea pigs produces a response comparable to that occurring in the human case, and that induced by the injection of human dengue blood in guinea pigs. While we are of the opinion that the anaerobic globular bodies described may bear etiological relationship to dengue, we realize that further proof and confirmation of our work are required to establish the connection.

1924 ◽  
Vol 40 (6) ◽  
pp. 817-833 ◽  
Author(s):  
William H. Harris ◽  
Charles W. Duval

The dengue cases studied during this epidemic were, as a whole, typical examples of the disease. The onset was sudden, often of a violent character, ushered in with severe headache and backache, vague pains throughout the body, and fever ranging from 101–105°F. On the 2nd or 3rd day a maculopapular eruption appeared, generally on the neck, chest, and arms, but sometimes more widely disseminated. In most instances the fever remained for 3 or 4 days, after which it dropped to normal to rise again in 24 to 48 hours. The secondary rise, while occasionally higher than the primary one, was as a rule of a milder character. A few cases occurred in which marked jaundice existed. As reported for previous epidemics, no fatalities were recorded and hence no human material for histological study was available. Those cases caught in the fastigium of the disease were selected when possible as a source of material. The leucocytic count in all of the observed human cases was below normal. The experiments herein reported upon the transmission of dengue fever to the guinea pig are based upon the use of material secured from sixteen typical human cases of the disease, and upon the inoculation of many animals. Of the 143 animals used for the initial transmission, 42, representing eleven human cases out of the sixteen studied, reacted in a characteristic manner. The reaction occasioned in these animals by the inoculations closely resembles the symptoms seen in human dengue, differing only in the absence of exanthem. The primary pyrexia following regularly after a definite incubation period of 2 to 5 days, the secondary rise in temperature after a 24 to 48 hour remission ("saddleback"curve), and the concomitant fall in the circulating leucocytes present a syndrome identical with that of the human disease. Dark-field and special tinctorial studies of the dengue material, both human and experimental, have failed to reveal any visible spirochetal microorganism. It seems unlikely that an organism of any proportion other than a minute body is the excitant of dengue fever. In the experimentally induced infection of the guinea pigs by the inoculation of dengue virus there occurs a rather constant and characteristic gross alteration of the lymphoid tissues, and of the spleen especially, which latter organ often attains a size three to four times that of the normal. Enlarged lymph glands in the peritoneal areas are also a fairly constant finding. The adrenal glands occasionally show marked enlargement. The histopathology consists of an endothelial proliferation occurring chiefly in connection with the Malpighian bodies of the spleen and the germinal centers of the lymph nodes. Experiments performed with a view of demonstrating the protection afforded the recovered guinea pig were somewhat confused by delayed fatalities or later intercurrent infections to which the dengue-inoculated animal seems highly susceptible. The constant and uniform results for all the positive cases indicate that the virus of dengue fever is not only transmissible to the guinea pig but is susceptible to propagation in this species through an undetermined number of successive generations. After certain of the virus strains had been propagated through four or more generations they were discontinued. Two strains, however, have been continued for 36 and 45 generations respectively. The equally successful results with Berkefeld filtered material and whole defibrinated blood indicate that the excitant of dengue fever belongs in the group of filterable viruses.


1920 ◽  
Vol 32 (5) ◽  
pp. 601-625 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler

Injections into guinea pigs of the blood and the emulsions of liver and kidney obtained at autopsy from a fatal case of yellow fever in Merida induced in some of these animals, after a period of several days incubation, a rise of temperature which lasted 1, 2, or more days. When killed for examination at this febrile stage the animals invariably showed hemorrhagic areas of various size, sometimes few and sometimes numerous, in the lungs, and also, though less constantly, in the gastrointestinal mucosa, together with general hyperemia of the liver and kidneys. In a guinea pig (No. 6) inoculated with the liver emulsion of Case 1 there was a trace of jaundice on the 9th day. Injections of the blood or liver and kidney emulsions from such animals into normal guinea pigs reproduced the febrile reactions and the visceral lesions. The majority of the animals which were allowed to live and complete the course of the infection rapidly returned to normal (within several days). Examinations of these surviving guinea pigs after 2 weeks revealed the presence of rather old hemorrhagic foci in the lungs. In the course of further attempts to transfer the passage strain, a secondary infection by a bacillus of the paratyphoid group caused many deaths among the guinea pigs and resulted finally in the loss of the strain from Case 1. Most of the cultures made with the heart's blood taken at autopsy from Case 1 proved to be contaminated with a bacillus of the coli group. The contents of the apparently uncontaminated tubes were inoculated into guinea pigs, but the results were for the most part negative or vitiated by a secondary infection. Dark-field search for the leptospira with the autopsy materials was negative, although prolonged and thorough examination was not practicable at the time of these experiments. Our efforts were concentrated on obtaining positive animal transmission rather than on the time-consuming demonstration of the leptospira, which when unsuccessful does not necessarily exclude the presence of the organism in small numbers. Likewise, the dark-field work with the material from guinea pigs was confined to a brief examination and was omitted in many instances. Under these circumstances no leptospira was encountered in any of the material from Case 1. On the other hand, the results obtained with the specimens of blood from Case 2 were definitely positive, not only in the transmission of the disease directly, or indirectly by means of cultures, into guinea pigs, but also in the demonstration of the leptospira in the primary cultures and in the blood and organ emulsions of guinea pigs experimentally infected with such cultures. Definite positive direct transmissions were obtained with the specimens of blood drawn on the 2nd and 3rd days. No blood was taken on the 4th or 6th days. There were indications of abortive or mild leptospira infection in the guinea pigs inoculated with the blood taken on the 5th day. Regarding the inoculation of cultures from Case 2, it may be stated that only the cultures (leptospira +) made with the blood drawn on the 2nd day caused a definite fatal infection in guinea pigs. From this series a continuous passage in the guinea pig has been successfully accomplished. One of the guinea pigs (No. 48) inoculated with the culture 5 days old (leptospira +) made from the blood taken on the 3rd day presented typical symptoms, and a positive transfer from this to another animal (No. 98) was also made. Cultures of the blood drawn on the 5th and 7th days gave unsatisfactory results, owing to a secondary contamination. Leptospiras were detected in some of the culture tubes containing 2nd and 3rd day specimens of blood from Case 2; they were few in number and for the most part immotile, owing perhaps to some unfavorable cultural condition such as a fungus contamination. Charts 17, 18, and 19 give a summary of the experiments. See PDF for Structure


1930 ◽  
Vol 52 (2) ◽  
pp. 195-199 ◽  
Author(s):  
M. Ruiz Castaneda

The experiments recorded above have demonstrated the following points: 1. Scrotal swelling can appear in guinea pigs directly inoculated from a human case of Mexican typhus fever. 2. In certain strains of this disease, a number of generations of guinea pigs may show absolutely no scrotal swelling, which, however, may reappear in subsequent animals, suggesting—though not absolutely proving—that the scrotal swelling is an integral part of the disease and is not due to an incidental accompanying organism. If the latter were true, one would expect the organisms that caused the scrotal swelling to disappear during the negative generations. 3. A typhus fever sustained by a guinea pig without scrotal swelling protects against the swelling upon subsequent inoculation with a strain which produces this with considerable regularity. 4. Louse passage increases the capacity of a strain to produce the scrotal lesion, probably because of the considerable accumulation of rickettsia in the louse, but in the experiment noted, even after louse passage, two generations without swelling occurred, followed by reoccurrence of the swelling. We believe that these observations, taken together, can be interpreted in favour of the likelihood that the swelling is a part of the disease and that the rickettsia-like organisms described by Mooser in the tunica vaginalis have etiological significance.


2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P101-P101
Author(s):  
Timothy J Hughes ◽  
Gregory J Matz ◽  
Sam J Marzo

Problem Human case reports have been published demonstrating a rapidly progressive sensorineural hearing loss associated with overuse or abuse of acetaminophen/hydrocodone. We hypothesized that hearing loss would result in the guinea pig model if given high, chronic doses of this drug. Methods Sixty female, pigmented guinea pigs were randomly assigned to a control, acetaminophen, hydrocodone, or acetaminophen/hydrocodone group. All guinea pigs were tested with baseline ABRs on day 0, and post drug/placebo administration on days 30, 60, 90, and 120. At the end of the study 5 animals from each group were sacrificed and their cochleae were harvested for histological investigation. Results No significant change in threshold (dB) was seen between the 4 groups. Histological studies of the cochleae revealed no hair cell damage in any of the groups. Conclusion Hydrocodone and acetaminophen/hydrocodone do not have an obvious deleterious effect on guinea pig cochlear function or structure. Significance This study may indicate that human hearing loss seen with abuse of acetaminophen/hydrocodone is multi-factorial and not just related to the drug abuse alone.


1960 ◽  
Vol XXXV (II) ◽  
pp. 204-210 ◽  
Author(s):  
O. Castrén ◽  
L. Hirvonen ◽  
S. Närvänen ◽  
K. Soiva

ABSTRACT The permeability of the guinea pig placenta to progesterone was studied by injecting progesterone-4-14C intravenously into seven pregnant guinea pigs, and determining the levels of radioactivity in the plasma samples taken from the mothers and foetuses during 15 minutes after the injection. The ratio of the levels of radioactivity in the plasma of the foetus to the level in the plasma of the mother increased with time. In three experiments progesterone-4-14C was injected into the umbilical vein of one of the foetuses in the uterus. Radioactivity was measured in the plasma samples that were taken from the mother from 2 to 23 minutes after the injection. A low level of radioactivity was also found in some of the plasma samples taken from the other foetuses. These observations show that radioactive progesterone or its metabolites pass through the guinea pig placenta in both directions.


Author(s):  
Corazon D. Bucana

In the circulating blood of man and guinea pigs, glycogen occurs primarily in polymorphonuclear neutrophils and platelets. The amount of glycogen in neutrophils increases with time after the cells leave the bone marrow, and the distribution of glycogen in neutrophils changes from an apparently random distribution to large clumps when these cells move out of the circulation to the site of inflammation in the peritoneal cavity. The objective of this study was to further investigate changes in glycogen content and distribution in neutrophils. I chose an intradermal site because it allows study of neutrophils at various stages of extravasation.Initially, osmium ferrocyanide and osmium ferricyanide were used to fix glycogen in the neutrophils for ultrastructural studies. My findings confirmed previous reports that showed that glycogen is well preserved by both these fixatives and that osmium ferricyanide protects glycogen from solubilization by uranyl acetate.I found that osmium ferrocyanide similarly protected glycogen. My studies showed, however, that the electron density of mitochondria and other cytoplasmic organelles was lower in samples fixed with osmium ferrocyanide than in samples fixed with osmium ferricyanide.


1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.


1963 ◽  
Vol 43 (1) ◽  
pp. 110-118 ◽  
Author(s):  
R. Ekholm ◽  
T. Zelander ◽  
P.-S. Agrell

ABSTRACT Guinea pigs, kept on a iodine-sufficient diet, were injected with Na131I and the thyroids excised from 45 seconds to 5 days later. The thyroid tissue was homogenized and separated into a combined nuclear-mitochondrial-microsomal fraction and a supernatant fraction by centrifugation at 140 000 g for one hour. Protein bound 131iodine (PB131I) and free 131iodide were determined in the fractions and the PB131I was analysed for monoiodotyrosine (MIT), diiodotyrosine (DIT) and thyroxine after hydrolysis of PB131I. As early as only 20 minutes after the Na131I-injection almost 100% of the particulate fraction 131I was protein bound. In the supernatant fraction the protein binding was somewhat less rapid and PB131I values above 90% of total supernatant 131I were not found until 3 hours after the injection. In all experiments the total amount of PB131I was higher in the supernatant than in the corresponding particulate fraction. The ratio between supernatant PB131I and pellet PB131I was lower in experiments up to 3 minutes and from 2 to 5 days than in experiments of 6 minutes to 20 hours. Hydrolysis of PB131I yielded, even in the shortest experiments, both MIT and DIT. The DIT/MIT ratio was lower in the experiments up to 2 hours than in those of 3 hours and over.


1965 ◽  
Vol 20 (5) ◽  
pp. 1091-1093 ◽  
Author(s):  
Alfred Richtarik ◽  
Thomas A. Woolsey ◽  
Enrique Valdivia

A device for use in recording ECG's from guinea pigs is described. It is constructed of Plexiglas and consists of a base with four electrodes (separated by plastic ridges) on which the animal stands. The animal's activity is restricted by a removable box, the ends and top of which are adjustable to compensate for variations in animal size. The device permits recording of ECG's in rapid succession from quiet, unanesthetized animals in normal standing posture. Results obtained with the method are reported. apparatus for guinea pig ECG; time relations guinea pig ECG; normal ECG, guinea pig; factors affecting quality of ECG recordings from guinea pigs Submitted on October 21, 1964


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Yifang Yang ◽  
Junshu Wu ◽  
Defu Wu ◽  
Qi Wei ◽  
Tan Zhong ◽  
...  

Abstract Background The use of ocular hypotensive drugs has been reported to attenuate myopia progression. This study explores whether brimonidine can slow myopia progression in the guinea pig form-deprivation (FD) model. Methods Three-week-old pigmented male guinea pigs (Cavia porcellus) underwent monocular FD and were treated with 3 different methods of brimonidine administration (eye drops, subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for intravitreal injection (2 μg/μL, 4 μg/μL, 20 μg/μL, 40 μg/μL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure (IOP), refractive error and axial length (AL), respectively. On day 21, guinea pigs were sacrificed for RNA sequencing (RNA-seq) to screen for associated transcriptomic changes. Results The myopia model was successfully established in FD animals (control eye vs. FD eye, respectively: refraction at day 20, 0.97 ± 0.18 D vs. − 0.13 ± 0.38 D, F = 6.921, P = 0.02; AL difference between day 0 and day 21, 0.29 ± 0.04 mm vs. 0.45 ± 0.03 mm, F = 11.655, P = 0.004). Among the 3 different brimonidine administration methods, intravitreal injection was the most effective in slowing myopia progression, and 4 μg/μL was the most effective among the four different concentrations of brimonidine intravitreal injection tested. The AL and the refraction of the brimonidine intravitreal injection group was significantly shorter or more hyperopic than those of other 2 groups. Four μg/μL produced the smallest difference in AL and spherical equivalent difference values. FD treatment significantly increased the IOP. IOP was significantly lower at 1 day after intravitreal injections which was the lowest in FD eye of intravitreal injection of brimonidine. At day 21, gene expression analyses using RNA-seq showed upregulation of Col1a1 and Mmp2 expression levels by intravitreal brimonidine. Conclusions Among the 3 different administration methods, intravitreal injection of brimonidine was the most effective in slowing myopia progression in the FD guinea pig model. Intravitreal brimonidine at 4 μg/μL significantly reduced the development of FD myopia in guinea pigs. Expression levels of the Col1a1 and Mmp2 genes were significantly increased in the retinal tissues of the FD-Inj-Br group.


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