Anticoccidial effect of Origanum majoranum aqueous extract on Eimeria tenella-infected chicken.

Avian coccidiosis, an important protozoal disease of chicken triggered by coccidian protozoa of genus Eimeria, causes considerable economic losses to broiler producers. The study was designed to assess the efficiency of Origanum majoranum aqueous extract (OMAE) on E. tenella-infected broiler chicken. Birds were divided into four groups including: positive control (PC, challenged with 5×104 sporulated oocysts of E. tenella at the 12th day of age), PC+OMAE (challenged with E. tenella oocysts at the 12th day of age and received OMAE (125 mg/kg BW) orally, started at the 7th day of age, and continued for 14 consecutive days), OMAE (received OMAE (125 mg/kg BW) orally, at the 7th day of age, for 14 consecutive days), and negative control (received basal diet only). Anticoccidial efficacy of OMAE was evaluated by complete blood picture, serum chemistry, serum protein electrophoresis, antioxidants markers, cecal oocysts count, and cecal lesions score. Briefly, collected data indicated that supplementation of OMAE could increase antioxidants concentrations and improve changes in hematobiochemical parameters and serum protein fractions, as well as decrease cecal oocysts count and reduce cecal lesion scores in E. tenella-infected birds. In conclusion, OMAE restores oxidant-antioxidant balance, and its supplementation in broiler chicken can alleviate E. tenella-infection and reduce its severity.

Anticoccidial effect of Origanum majoranum aqueous extract on Eimeria tenella-infected chicken

@#Avian coccidiosis, an important protozoal disease of chicken triggered by coccidian protozoa of genus Eimeria, causes considerable economic losses to broiler producers. The study was designed to assess the efficiency of Origanum majoranum aqueous extract (OMAE) on E. tenella-infected broiler chicken. Birds were divided into four groups including: positive control (PC, challenged with 5×104 sporulated oocysts of E. tenella at the 12th day of age), PC+OMAE (challenged with E. tenella oocysts at the 12th day of age and received OMAE (125 mg/kg BW) orally, started at the 7th day of age, and continued for 14 consecutive days), OMAE (received OMAE (125 mg/kg BW) orally, at the 7th day of age, for 14 consecutive days), and negative control (received basal diet only). Anticoccidial efficacy of OMAE was evaluated by complete blood picture, serum chemistry, serum protein electrophoresis, antioxidants markers, cecal oocysts count, and cecal lesions score. Briefly, collected data indicated that supplementation of OMAE could increase antioxidants concentrations and improve changes in hematobiochemical parameters and serum protein fractions, as well as decrease cecal oocysts count and reduce cecal lesion scores in E. tenella-infected birds. In conclusion, OMAE restores oxidant-antioxidant balance, and its supplementation in broiler chicken can alleviate E. tenella-infection and reduce its severity.

Effect of Mouse Strain on Equine Herpesvirus 9 Infection.

The infectivity of equine herpesvirus (EHV)-9 has been studied in different animal models including immunocompromised animals. The current study focused on the infectivity of EHV-9 in different mouse strains (C3H, C57BL, DBA, BALB/c-nu/nu, BALB/c and ICR) by intranasal inoculation of 2 × 106 plaque forming units (PFU). Various organs, including head and lungs, were collected 7 days post infection (dpi) to investigate microscopical lesions and the distribution of EHV-9 antigen. Immunopositivity of tissue sections was scored using ImageJ software. Open reading frame (ORF) 30 expression in lung tissues was quantified using quantitative reverse transcriptase polymerase chain reaction. Pathological examination revealed different degrees of rhinitis in the different mouse strains. Severe rhinitis was detected in C3H and BALB/c-nu/nu strains, moderate rhinitis was observed in C57BL and DBA strains and no lesions were detected in BALB/c mice. Immunopositivity for EHV-9 antigens was detected in the olfactory epithelium of C3H and BALB/c-nu/nu strains. Compared with C57BL, DBA, BALB/c-nu/nu, ICR and BALB/c strains, the C3H strain showed greater expression of EHV-9 antigens in the brain. The proportion of areas with high positive to positive immunoreactivity for EHV-9 were 7.57, 3.42, 3.12, 2.51, 1.79 and 0.03% for C3H, C57BL, DBA, BALB/c-nu/nu, ICR and BALB/c strains, respectively. The proportions of areas with low positive to negative immunoreactivity were 92.42, 96.70, 96.87, 97.48, 98.16 and 99.96%, respectively. The highest relative expression levels for EHV-9 ORF30 in the lungs were in C3H mice. No significant differences in the expression of ORF30 were observed in other strains. In conclusion, of the strains examined, C3H, C57BL, DBA, BALB/c-nu/nu and ICR were the most susceptible to EHV-9 infection, and the BALB/c strain was less susceptible.

Onset of Inflammation With Ischemia: Implications for Donor Lung Preservation and Transplant Survival.

Lungs stored ahead of transplant surgery experience ischemia. Pulmonary ischemia differs from ischemia in the systemic organs in that stop of blood flow in the lung leads to loss of shear alone because the lung parenchyma does not rely on blood flow for its cellular oxygen requirements. Our earlier studies on the ischemia-induced mechanosignaling cascade showed that the pulmonary endothelium responds to stop of flow by production of reactive oxygen species (ROS). We hypothesized that ROS produced in this way led to induction of proinflammatory mediators. In this study, we used lungs or cells subjected to various periods of storage and evaluated the induction of several proinflammatory mediators. Isolated murine, porcine and human lungs in situ showed increased expression of cellular adhesion molecules; the damage-associated molecular pattern protein high-mobility group box 1 and the corresponding pattern recognition receptor, called the receptor for advanced glycation end products; and induction stabilization and translocation of hypoxia-inducible factor 1α and its downstream effector VEGFA, all of which are participants in inflammation. We concluded that signaling with lung preservation drives expression of inflammatory mediators that potentially predispose the donor lung to an inflammatory response after transplant.

Pathological findings in equine herpesvirus 9-induced abortion in rats.

Pregnant rats were infected experimentally with equine herpesvirus (EHV)-9, a new neurotropic equine herpesvirus serologically similar to EHV-1, during the first and third trimesters. The inoculated dams had mild to severe neurological signs and gave birth to dead fetuses or undersized pups. Rats inoculated during the first and last trimesters had varying degrees of encephalitis as well as abnormalities of the placentas in the form of marked dilation of maternal blood sinusoids and varying degrees of atrophy and necrosis of the trophoblast cells of the labyrinth, the spongiotrophoblasts and the giant cell layer. Virus antigen was detected by immunohistochemistry in the brain and the trophoblast cells of labyrinth, the spongiotrophoblasts and giant cell layer of the placenta in rats inoculated during the first trimester. Virus antigen was detected in fetuses from rats inoculated in the first and last trimesters. Virus DNA was amplified by polymerase chain reaction from the placenta and fetuses of inoculated rats. EHV-9 may induce fetal death and abortion in pregnant dams, possibly caused by direct EHV-9 infection of the placenta and/or fetus as well as the secondary effect of vascular injury.

Susceptibility of BALB/c-nu/nu mice and BALB/c mice to equine herpesvirus 9 infection.

This study aimed to clarify the timing and infectivity of equine herpesvirus 9 (EHV-9) infection in BALB/c-nu/nu mice and their immunocompetent counterpart (BALB/c). Following intranasal inoculation with 10(5) PFU of EHV-9, specimens from 8 mice per group were collected at different times postinoculation (PI) and assessed using histopathology, immunohistochemistry for viral antigen, and quantitative real-time polymerase chain reaction for ORF30 gene expression. In BALB/c-nu/nu mice, EHV-9 antigen was abundant in olfactory epithelia of all inoculated animals, and in the olfactory bulb of 1 animal. In contrast, only 1 BALB/c mouse per time point had rhinitis, with mild to moderate immunopositivity starting from 12 to 48 h PI, followed by a gradual virus clearance at 72 h PI. Statistically, significant differences were noted in the immunohistochemistry reactions between the 2 mouse strains, indicating that BALB/c-nu/nu is more susceptible to infection. Relative expression levels of ORF30 gene in olfactory epithelia were significantly different between the 2 groups, with the exception of 12 h PI, when BALB/c-nu/nu animals showed dramatic increases in ORF30 gene expression level until 48 h PI, followed by a decline in expression level until the end of experiment. In contrast, the expression level in brains showed no differences between mouse strain except at 96 h PI. In both strains, the highest messenger RNA expression was detected at 48 h PI, followed by a decline in BALB/c mice, proving a rapid clearance of virus in BALB/c and a gradual slowing down of the increased expression levels in BALB/c-nu/nu.

An ocular infection model using suckling hamsters inoculated with equine herpesvirus 9 (EHV-9): kinetics of the virus and time-course pathogenesis of EHV-9-induced encephalitis via the eyes.

By using a new member of the neurotropic equine herpesviruses, EHV-9, which induced encephalitis in various species via various routes, an ocular infection model was developed in suckling hamsters. The suckling hamsters were inoculated with EHV-9 via the conjunctival route and were sacrificed after 6, 12, 24, 36, 48, 72, 96, 120, and 144 hours (h) post inoculation (PI). Three horizontal sections of the brains, including the eyes and cranial cavity, were examined histologically to assess the viral kinetics and time-course neuropathological alterations using a panoramic view. At 6 to 24 h PI, there were various degrees of necrosis in the conjunctival epithelial cells, as well as frequent mononuclear cell infiltrations in the lamina propria and the tarsus of the eyelid, and frequent myositis of the eyelid muscles. At 96 h PI, encephalitis was observed in the brainstem at the level of the pons and cerebellum. EHV-9 antigen immunoreactivity was detected in the macrophages circulating in the eyelid and around the fine nerve endings supplying the eyelid, the nerves of the extraocular muscles, and the lacrimal glands from 6 h to 144 h PI. At 96 h PI, the viral antigen immunoreactivity was detected in the brainstem at the level of the pons and cerebellum. These results suggest that EHV-9 invaded the brain via the trigeminal nerve in addition to the abducent, oculomotor, and facial nerves. This conjunctival EHV-9 suckling hamster model may be useful in assessing the neuronal spread of neuropathogenic viruses via the eyes to the brain.

Kinetics and pathogenicity of oral infection by equine herpesvirus-9 in mice and suckling hamsters.

The pathogenesis and kinetics of oral infection by equine herpesvirus (EHV)-9 were studied in mice and hamsters. After oral inoculation of 10(5) plaque-forming units (PFU) of virus, 1-week-old suckling hamsters showed varying severity of neurological disease from 72 hours post inoculation (hpi) and all of these animals had died by 96 hpi. Four-week-old ICR mice inoculated orally with 4 × 10(4)PFU of virus showed no clinical signs, but they developed erosive and ulcerative gastritis from 36 hpi. Varying degrees of encephalitis were seen in infected mice and hamsters, and the hamsters also developed myelitis by 96 hpi. Immunohistochemistry performed on whole body sections of suckling hamsters revealed the kinetics of spread of the virus to the central nervous system. EHV-9 antigen was detected initially in macrophages of the oral and lingual submucosa. At 36 hpi virus antigen was detected in the nerve fibres and pseudounipolar neurons of the trigeminal ganglion and at 96 hpi antigen was present in the myenteric plexuses of the intestine. Virus antigen was also detected in the liver, lungs and heart of affected animals. EHV-9 DNA was detected by polymerase chain reaction in the brain, blood and spinal cord of suckling hamsters at 36, 48 and 96 hpi. These findings show that EHV-9 may spread via the trigeminal nerve when mice and hamsters are inoculated orally with virus.

Kinetics and pathogenicity of equine herpesvirus-9 infection following intraperitoneal inoculation in hamsters.

The kinetics of infection and pathogenicity of equine herpesvirus-9 (EHV-9) was studied in a hamster model. Five-week-old Syrian hamsters and 5-day-old suckling hamsters were inoculated intraperitoneally with 10(5) and 4×10(4) plaque-forming units of EHV-9, respectively. EHV-9 antigens were detected by immunocytochemistry in the peritoneal macrophages, which may be the primary site of virus attachment and propagation at 6h post inoculation (hpi). At 12 hpi, viral antigen was observed in the abdominal nerves and ganglia (mainly the coeliac ganglia). Virus antigen was detected in the dorsal root (spinal) ganglia, in parts of the spinal cord (particularly the mid-lumbar area) and in the myenteric plexuses at 36, 48 and 72 hpi, respectively. At 96 hpi, virus antigen was detected in the most caudal part of the brain. Polymerase chain reaction conducted on samples of the blood, spinal cord and brain revealed EHV-9 DNA in the spinal cord at 36 hpi and in the blood at 48 hpi and for 4 days after this initial detection. It is suggested that after initial propagation in the abdominal macrophages, EHV-9 infected the abdominal ganglia or myenteric plexuses and then travelled to the brain via the peripheral nerves and spinal cord. Examination of other organs also revealed the presence of EHV-9, suggesting that the virus might infect tissues other than those of the nervous system.

Effects of equine herpesvirus-9 infection in pregnant mice and hamsters.

The pathogenicity of equine herpesvirus (EHV)-9, a new neurotropic equine herpesvirus isolated from gazelles, was assessed in pregnant rodents (mice and hamsters) following intranasal inoculation. The pregnant female mice and hamsters were inoculated with EHV-9 in the early or late trimesters. The inoculated animals exhibited mild to severe neurological signs and gave birth to dead or undersized fetuses. All three mice and four hamsters inoculated in the first trimester had varying degrees of placental abnormality, characterized by markedly dilated maternal blood sinusoids, atrophy of the trophoblast cells and necrosis of the middle layer of the trophoblast. There was also endometrial blood vessel congestion and necrosis and disorganization of the fetal capillaries in the mice and hamsters inoculated in the last trimester. EHV-9 antigen was detected in the brain of dams and the lungs of the fetuses and in the middle of the trophoblast layer of the placenta in hamsters inoculated in the first trimester. The placental lesions were milder in mice than in the hamsters. The mice and hamsters inoculated in the last trimester had more prominent lesions than the animals inoculated in the first trimester. These results suggest that EHV-9 can cause the death of the fetus or abortion and that these events may be secondary to placental vascular compromise.

Study on the infectivity of equine herpesvirus 9 (EHV-9) by different routes of inoculation in hamsters.

The infectivity and pathology of equine herpesvirus 9 (EHV-9), a new neurotropic equine herpesvirus isolated from gazelles, was studied in hamsters experimentally infected via nasal, ocular, oral, intravenous (IV), or peritoneal routes. Clinically, all animals inoculated by the nasal route and ~25% inoculated by the oral and peritoneal routes showed neurological signs on days 3, 6, and 9 postinoculation (PI), respectively. Neurological signs were not observed in animals administered EHV-9 by the IV and ocular routes. With the exception of animals administered EHV-9 by the IV route, all infected animals had lymphocytic meningoencephalitis. Although there were a number of differences in the severity and distribution of the lesions depending on the route of inoculation, the basic features of lymphocytic meningoencephalitis caused by EHV-9 were common. Lesions consisted of neuronal necrosis, perivascular aggregates of lymphocytes, plasma cells, and neutrophils, gliosis, intranuclear inclusion bodies, and diffuse lymphocytic infiltrates in the meninges. Viral antigen was detected in degenerated neurons in infected animals inoculated by the nasal, ocular, oral, and peritoneal routes. The distribution of EHV-9 antigen was somewhat dependent on inoculation route. There were no microscopic abnormalities or viral antigen in animals treated by the IV route. This study provides new data about experimental EHV-9 infection in hamsters through routes other than the IV route. These results suggest that in the animals infected by the oral, ocular, and peritoneal routes, EHV-9 might travel to the brain through nerves, other than by the olfactory route, after initial propagation at the site of viral entry.

Acute respiratory distress syndrome among trauma patients: trends in ICU mortality, risk factors, complications and resource utilization.

OBJECTIVE: To evaluate trends in mortality and related factors among trauma patients who developed acute respiratory distress syndrome (ARDS). STUDY: Observational study based on data prospectively gathered in computerized trauma registry. SETTING: Trauma intensive care unit (ICU) of 48 beds in level I trauma center. PATIENTS: All trauma patients with ARDS admitted during 1985-87 (486, group 1 [G1]) and 1993-95 (552, group 2[G2]). METHODS: ARDS was defined by American-European Consensus Conference criteria and the need for 48 h or more on mechanical ventilation with FIO2 greater than 0.50 and PEEP of more than 5 cmH2O. Demographics, severity score, injury-admission delay time, first 24-h transfusion and septic and organ system failure complications were independent variables. ICU mortality was the dependent variable. ICU length of stay (LOS) and life support techniques were considered. Respiratory and renal support strategies were different in the two time periods. RESULTS: Mortality decreased over the period (G1: 29.2% vs G2: 21.4%, p < 0.04), in patients aged both over and under 65 years. Multivariate analysis showed mortality was related to age, severity and time period (G1 1.68-fold that in G2) and that the greater G1 mortality was related to more renal failure and hematologic failure/dysfunction. ICU LOS decreased from 31.7+/-26.7 days (G1) to 27.3+/-22 days (G2) (p < 0.003). CONCLUSIONS: Mortality among trauma patients with ARDS declined over the 8 years studied and was associated with less organ failure. This reduction was probably the result of new approaches to mechanical ventilation, renal failure replacement and vasoactive drug therapy.

Airway pressure release ventilation: theory and practice.

Airway pressure release ventilation (APRV) is a relatively new mode of ventilation, that only became commercially available in the United States in the mid-1990s. Airway pressure release ventilation produces tidal ventilation using a method that differs from any other mode. It uses a release of airway pressure from an elevated baseline to simulate expiration. The elevated baseline facilitates oxygenation, and the timed releases aid in carbon dioxide removal. Advantages of APRV include lower airway pressures, lower minute ventilation, minimal adverse effects on cardio-circulatory function, ability to spontaneously breathe throughout the entire ventilatory cycle, decreased sedation use, and near elimination of neuromuscular blockade. Airway pressure release ventilation is consistent with lung protection strategies that strive to limit lung injury associated with mechanical ventilation. Future research will probably support the use of APRV as the primary mode of choice for patients with acute lung injury.

Hyperlactatemia, increased osmolar gap, and renal dysfunction during continuous lorazepam infusion.

OBJECTIVE: To review effects of the vehicle of lorazepam, propylene glycol, in regard to lactate, osmolarity, and renal dysfunction. DESIGN: Case report. SETTING: Intensive care unit of a Level I trauma center. Patient A 36-yr-old Hispanic man who developed severe respiratory failure and required high-dose lorazepam for sedation. The patient was ventilated with low tidal volumes in a lung-protective fashion, with resultant "permissive hypercapnia." Lactates and osmolalities rose on initiation and fell, as expected, on discontinuation of the lorazepam infusion. However, there was no renal compensation for the hypercapnia except while the patient was not receiving lorazepam. MEASUREMENTS AND MAIN RESULT: Serial osmolalities, lactates, serum bicarbonate, PaCO2, and pH were measured during lorazepam infusion. Rise and fall of serum lactate and osmolality closely correlated with lorazepam. Serum bicarbonate rose significantly while the patient was not receiving lorazepam in response to hypercarbia and failed to rise while the patient was receiving lorazepam. CONCLUSION: The vehicle of lorazepam, propylene glycol, can cause hyperlactatemia and elevated osmolar gaps. However, propylene glycol may also interfere with renal tubular function and may blunt renal compensation for respiratory acidosis.

Extracorporeal support in an adult with severe carbon monoxide poisoning and shock following smoke inhalation: a case report.

The objective of this study was to discuss the case of a patient with severe smoke inhalation-related respiratory failure treated with extracorporeal support. The study was set in a 12-bed multi-trauma intensive care unit at a level one trauma center and hyperbaric medicine center. The patient under investigation had carbon monoxide poisoning, and developed acute respiratory distress syndrome and cardiovascular collapse following smoke inhalation. Rapid initiation of extracorporeal support, extreme inverse-ratio ventilation and intermittent prone positioning therapy were carried out. Admission and serial carboxyhemoglobin levels, blood gases, and computerized tomography of the chest were obtained. The patient developed severe hypoxia and progressed to cardiovascular collapse resistant to resuscitation and vasoactive infusions. Veno-venous extracorporeal support was initiated. Cardiovascular parameters of blood pressure, cardiac output, and oxygen delivery were maximized; oxygenation and ventilation were supported via the extracorporeal circuit. Airway pressure release ventilation and intermittent prone positioning therapy were instituted. Following 7 days of extracorporeal support, the patient was decannulated and subsequently discharged to a transitional care facility,neurologically intact. Smoke inhalation and carbon monoxide poisoning may lead to life-threatening hypoxemia associated with resultant cardiovascular instability. When oxygenation and ventilation cannot be achieved via maximal ventilatory management, extracorporeal support may prevent death if initiated rapidly.

Interhospital transport of the extremely ill patient: the mobile intensive care unit.

BACKGROUND: Critically ill patients may require specialized care that is offered only at tertiary referral centers. As regionalization and specialization of critical care become more common, transportation of critically ill patients must be refined. Transportation of critically ill patients within a hospital, much less outside the hospital, is often deemed unsafe because of medical instability. We report, here, our results from 2 yrs' experience of transporting extremely ill patients with respiratory failure via a ground critical care transport service. METHODS: A mobile intensive care unit was equipped and staffed to nearly recreate the intensive care environment. Staffing included a physician, nurse, respiratory therapist, and driver--all with extensive critical care experience. The mobile intensive care unit was equipped with a full pharmacy, advanced ventilatory equipment, and capability for full invasive hemodynamic monitoring. Data were analyzed by retrospective review. The predicted mortality rate, based on Pao2/Fio2 ratios, was compared with the actual mortality rate. RESULTS: During a 2-yr period, 39 critically ill patients were transported. Thirty-six of the 39 were candidates for extracorporeal lung assist, with a mean positive end-expiratory pressure requirement of 15.9, a mean Fio2 requirement of .93, and a mean Pao2/Fio2 ratio of 59.8. Pulmonary arterial catheters and peripheral arterial catheters were in place in 66.6% and 72% of patients, respectively. Vasoactive medications were being infused in 56%, and 74% were receiving medical paralytics. One patient died during movement from the bed to the transport gurney. Other than one episode of transient hypotension, there were no complications or untoward outcomes related to transport. Unique therapeutic interventions were performed at the receiving facility on 34 of 39 patients. The predicted mortality rate, based on indicators of lung dysfunction, was 68% to 100%; the actual subsequent hospital mortality rate was 43%. CONCLUSIONS: When a mobile intensive care unit is properly staffed and equipped and patient stabilization is performed before transfer, severely ill patients with respiratory failure can be transferred safely. For patients with respiratory failure, there may be a survival advantage in transfer to regional centers of expertise.

Life-threatening acute systemic lupus erythematosus: survival after multiple extracorporeal modalities: a place for the multipotential extracorporeal service.

Diffuse alveolar hemorrhage secondary to systemic lupus erythematosus (SLE) may cause life-threatening respiratory failure and may be associated with multiple organ failure. Extensive support may be necessary to sustain life while systemic therapy becomes effective. We report here a patient with profound respiratory failure secondary to SLE associated with multiorgan failure, who was supported with veno-arterial extracorporeal lung assist (ECLA), veno-venous ECLA, and multiple continuous renal replacement therapies during plasmapheresis. The full spectrum of extracorporeal life support and treatment modalities was performed seamlessly by a single service within the critical care department.

Veno-venous extracorporeal lung assist with concurrent distal aortic perfusion: repair of ruptured aorta in a patient with dense ARDS.

Extracorporeal lung assist (ECLA) allowed surgical repair of a ruptured descending thoracic aorta to be performed in a patient with profound respiratory failure. Dense acute respiratory distress syndrome (ARDS) developed during his 15-day hospitalization at a regional trauma center. After transfer to a Level I facility, an additional injury was diagnosed: traumatic rupture of the aorta, contained within a pseudoaneurysm. ECLA by the veno-venous route was required immediately preoperatively and distal aortic perfusion was performed during the aortic repair. Despite deflation of the left lung, the patient was oxygenated and ventilated adequately during surgery. Cross-clamp time was 48 minutes. The patient was weaned from ECLA by the fifth postoperative day. To our knowledge, this is the first report of concurrent veno-venous pulmonary support with distal aortic perfusion.