[Characteristics of gastric neuroendocrine tumors and the PDX-1 transcription factor expression]. / Kharakteristika neiroendokrinnykh opukholei zheludka i ekspressiya v nikh transkriptsionnogo faktora PDX-1.

OBJECTIVE: To study the features of gastric neuroendocrine tumors (NETs) and the diagnostic and prognostic significance of PDX-1 expression in them. MATERIAL AND METHODS: 207 NETs identified in 56 men and 115 women (59 had multiple NETs), and 94 cases of gastric cancer (comparison group) were studied morphologically and immunohistochemically. RESULTS: In more than half of the cases (54.93%), NETs were localized in the body of the stomach; the cardiac and antral parts of the stomach accounted for 8.64% and 11.73%, respectively. NETs of the cardiac region predominated in men, and of the body and antrum - in women. NETs of the cardiac region predominated in men, and of the body and antrum - in women. The vast majority of NETs were highly differentiated (89.20%), of which Grade 1, 2 and 3 were 55.41%, 40.76% and 3.82%, respectively. Neuroendocrine carcinomas (NEC) accounted for 10.80% of all NET cases. NECs were more often localized in the cardiac part of the stomach and accounted for 35.71% of all NETs in the cardiac part. The share of NEC among all NETs of the antrum was 15.79%, of the body of the stomach - only 3.37%. Metastases were found in 17.90% of NETs. Expression of PDX-1 was detected in 44.73% of NETs, 70% of NECs and 74.50% of gastric cancers. CONCLUSION: PDX-1 is involved in the mechanisms of precancerous and cancerous lesions of the stomach and its overexpression is detected in the majority of the most malignant NETs and gastric cancers.

[Ectopic acromegaly due to bronchial neuroendocrine tumors: the first description in Russia of three clinical cases].

 Acromegaly is a neuroendocrine disorder caused by excessive production of growth hormone (GH). In the majority of cases the cause of acromegaly is a pituitary tumor producing GH. Cases of ectopic acromegaly are much rarer. Ectopic acromegaly occurs in cases of tumors which produce growth hormone-releasing hormone (GHRH) or extrapituitary tumors which produce GH. The main sources of excessive GHRH production are neuroendocrine tumors (NETs) of the lung or pancreas. Treatment of ectopic acromegaly consists of surgical removal of the source of GHRH hyperproduction and in cases where surgery is not an option, somatostatin analogues, pegvisomant, chemotherapy, immunotherapy or radiation therapy are used.In this article three cases of ectopic acromegaly due to GHRH-producing lung NETs are presented, each of them being notable for a number of features. In the first two cases, clinical symptoms were mild, besides in the second case ectopic acromegaly was accompanied by primary hyperparathyroidism. In the third case ectopic acromegaly was accompanied by pituitary macroadenoma, and after surgical removal of the lung NET remission of acromegaly was not achieved. In all three cases, lung NETs were detected incidentally on radiologic chest screening for other conditions.

[Diagnostic value of bilateral inferior petrosal sinus sampling in various modifications and methods of radiation and radionuclide imaging in the diagnosis and differential diagnosis of ACTH-dependent endogenous hypercortisolism].

AIM: To analyze the diagnostic performance of bilateral inferior petrosal sinus sampling (BIPSS) with desmopressin as a stimulation agent and prolactin measurements to control catheter position with or without the ACTH/prolactin normalized ratio calculation in the differential diagnosis of ACTH-dependent endogenous hypercortisolism, and the diagnostics performance of ectopic ACTH-syndrome (EAS) visualization. MATERIALS AND METHODS: A single-center diagnostic study with a retrospective analysis of the data was carried out. The study included patients with ACTH-dependent endogenous hypercorticism with no visualization of pituitary adenoma on MRI or adenoma sizes less than 6 mm. All patients underwent BIPSS with and without calculation of the ACTH/prolactin normalized ratio. Visualization of an EAS included pituitary MRI (to exclude EAS), whole-body CT scan with contrast, and somatostatin receptor scintigraphy with 99mTc-Tectrotide and CT (99mTc-Tectrotide SPECT). The final verification was based on immunohistochemical confirmation of the tumor or stable remission of Cushing's disease (CD) after surgical treatment. Statistical data processing was carried out by using IBM SPSS Statistics 23. Confidence intervals were calculated using the JavaStat online calculator. RESULTS: 230 BIPSS were performed in 228 patients (166 women, 62 men), of which 178 patients were verified as CD and 50 cases were EAS of various localization. The effectiveness of catheterization of petrosal sinuses was 96.9%. The sensitivity of BIPSS without ACTH/prolactin ratio calculation (n=70) was 95.9% (95% CI 86.3-98.9), specificity was 92% (95% CI 75.0-97.8), for the BIPSS with additional determination of ACTH/prolactin-normalized ratio (n=51) - 97.3% (95% CI 86.2-99.5) and 93.8% (95% CI 71.7-98.9), respectively. The use of the MRI method for this sample of patients had a sensitivity of 60.2% (95% CI 52.6-67.5), specificity of 59.2% (95% CI 44.2-73.0), the total body CT with contrast has a sensitivity of 74% (95% CI 59.7-85.4), specificity of 100% (95% CI 97.95-100). The diagnostic accuracy for 99mTc-Tectrotide SPECT in NET visualization has a sensitivity of 73.3% (95% CI 44.9-92.2), specificity of 100% (95% CI 95.3-100). CONCLUSION: BIPSS with desmopressin stimulation and prolactin measurements to control catheter position, as well as the additional calculation of the ACTH/prolactin-normalized ratio, is an optimal method for the differential diagnosis of EAS. Patients who are identified an EAS on BIPSS may be further referred for 99mTc-Tectrotide SPECT and CT for tumor visualization.

[Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland]. / Skleroziruyushchii mukoepidermoidnyi rak shchitovidnoi zhelezy s eozinofiliei stromy.

Sclerosing mucoepidermoid carcinoma with stromal eosinophilia of thyroid gland is represented less than 100 cases in the world literature. We present a rare case of sclerosing mucoepidermoid carcinona with stromal eosinophilia in a 69-year-old woman who has been observed for multinodular goiter for more than 3 years. Cytological examination revealed a picture most of all corresponding to a malignant neoplasm (Bethesda V). The patient underwent a thyroidectomy. Pathomorphological examination revealed a neoplasm of mixed structure with foci of cribriform structures and squamous metaplasia with areas of keratinization. According to the IHC study, the expression of TTF-1, p63, cytokeratins 5/6 were positive, while there were no expression of thyroglobulin with its positive reaction in the thyroid tissue. Additional histochemical staining with Alcian blue revealed a positive reaction with a homogeneous acellular substance of the tumor. A comprehensive morphological study with the use of additional stains made it possible to accurately establish the diagnosis, which will determine the further tactics of managing the patient.

[Casuistic cases of parathyroid carcinoma with a verified mutation in the MEN1 gene].

Parathyroid cancer (PTC) is usually sporadic; however, it could be presented as a component of hereditary syndromes. The prevalence of PTC among patients with primary hyperparathyroidism (PHPT) is about 1% cases. The lack of reliable preoperative predictors significantly complicates the diagnosis of PTC. The clinical course is non-specific and in most cases is determined by severe hypercalcemia. The final diagnosis can only be made on the basis of invasive histopathologic features, while an analysis immunohistochemical (IHC) one can be used only as an additional method. Given the rarity the diagnosis of MEN1-related PTC a challenge. We present two clinical cases of patients with PTC and a verified heterozygous mutation in the MEN1 gene. The described cases demonstrate the complexity of morphological diagnosis for PTC, the heterogeneity of clinical manifestations in patients with the MEN1 mutation, as well as the need for timely screening to identify other components of MEN1 syndrome and mutations of the MEN1 gene among first-line relatives.

Prevalence of causative agents of transmissive tick-borned ricketsious in the Crimean peninsula.

The paper presents the results of a study of the prevalence of Ixodid ticks - potential carriers of tick-borne rickettsiosis pathogens. Ectoparasites were collected in various natural and climatic zones of the Crimean Peninsula within the year 2016-2018. As a result of screening with the help of real-time PCR analysis (PCR-RT), a genetic marker (a section of the gltA gene) of the rickettsia group of tick-borne spotted fever was detected in ticks. The most common DNA marker of rickettsia was found in ticks in the eastern regions of the steppe zone - 50,6 %, in the north-western part of the steppe zone this value was 12,0 %. The least amount of rickettsia target DNA was detected in ticks collected in the mountain forest and south bank zones - 4,5 %. As a result of sequencing of positive DNA samples from fragments of the gltA, ompA, ompB, and sca4 genes, the species composition of rickettsias was established. The DNA of 8 species of rickettsia was identified: Circulation of three R. conorii, R. massiliae, R. sibirica subsp. mongolotimonae, R. slovaca, R. aeschlimannii, R. monacensis, R. helvetica, R. raoultii. R. massiliae, R. slovaca, and R. helvetica were established in the Crimean Peninsula for the first time. The peculiarities of the geographical distribution of the identified rickettsia species were determined, which was due to the spread of mites-carriers of pathogens. The revealed diversity of rickettsia species and their vectors, due to the isolation of the areas of the main feeding animals and the established routes of migratory birds, suggests the circulation of other rickettsia species on the territory of the Crimean Peninsula. The obtained results suggest that the diseases of tick-borne rickettsiosis in the Crimean Peninsula can be caused not only by R. conorii, as previously thought, but also by other types of rickettsii.

Cases of Q fever detected in residents of the novosibirsk region hospitalized with suspection of infections transmitted by ticks.

Coxiella burnetii is the causative agent of Q fever (coxiellosis), which, in addition to acute manifestations, often occurs in a latent form, is prone to chronic course and, in the absence of antibiotic therapy, has a high risk of disability or death. As a result of the presence of a wide range of clinical manifestations specific to other infectious diseases, the use of laboratory test methods (LTM) is required to make a diagnosis. The presence of Q fever anthropurgic foci in the Novosibirsk region was described in the 90s of the last century, but due attention to its laboratory diagnostics is not paid in this region. The aim of the study was to identify genetic and serological markers of the causative agent, C. burnetii, in patients of the Novosibirsk region who were admitted for treatment with fever with suspected tick-borne infections (TBIs). DNA marker of the causative agent of Q fever was detected in blood samples by real time PCR in 9 out of 325 patients. In three patients, the presence of C. burnetii DNA was confirmed by sequencing of the IS1111 and htpB gene fragments. In ELISA tests, antibodies against the causative agent of coxiellosis were detected in the blood sera of 4 patients with positive results of PCR analysis. Contact with tick was registered in 7 out of 9 patients who had C. burnetii DNA and lacked markers of other TBIs. Six people were infected in the Novosibirsk region, two suffered from tick's bite in Altai, and one case was from the Republic of Kyrgyzstan. Thus, a complex approach using both PCR analysis and ELISA provided the identification of markers of the Q fever causative agent in patients admitted with suspected TBIs, thereby differentiating it from other infections. Contact with ticks in most cases suggests that infection with C. burnetii had a transmissible pathway.

Indication Q fever pathogen in the south of Far east.

Q fever (coxiellosis) is a widespread natural focal disease in the world. The causative agent of coxiellosis is the gram-negative bacterium Coxiella burnetii, which is highly contagious and low virulence. The main carriers of C. burnetii are ixodid ticks, which feed on domestic and farm animals in anthropurgic foci. To address the possible circulation of the Q fever pathogen in the territory of the Primorsky Territory, 334 samples of various natural material collected in the spring-summer period of 2019 were studied. In the vicinity of the Vladivostok (on Reineke island), genetic markers of C. burnetii were detected in 19.7% of all tick species. In the Khankaisk region, coxiella DNA was detected more often (in 6.3%) in ticks of D. silvarum, in ticks of I. persulcatus and H. japonica, 1 case was detected. From 56 copies. ixodid ticks sucked to humans, C. burnetii DNA was detected in ticks of I. persulcatus in 38.8%, H. concinna - in 14.3%. In the serum of farm animals, the presence of coxiella in sheep in 3 samples was detected, in horses - in two. Sequencing of the obtained sequences showed the presence of the pathogen C. burnetii in the blood serum of animals. The ticks have stuck to people in 6 samples were identified C. burnetii and 6 samples - Coxiella-like endosymbiont. The presented results indicate the circulation of the causative agent of Q fever in the territory of the Primorsky Territory. To obtain a more complete description of the current epidemiological situation, it is necessary to conduct more extensive studies of natural material and blood of people with suspected Q fever.

The role of Rhipicephalus sanguineus ticks parasitizing dogs in the spread of tick-borne rickettsial pathogens in the city of Sevastopol.

The occurrence of Mediterranean fever with periods of increase and decrease has been recorded in the Crimean peninsula. The city of Sevastopol and its vicinity are known endemic areas for this disease. Some of the most active agents in the spread of this rickettsiosis are feral and abandoned dogs. The aim of this study was to test ticks parasitizing dogs in Sevastopol for the presence of Rickettsia using molecular methods. The testing of ticks was carried out using real-time PCR and the 'Real Best DNA Rickettsia species' kit (AO 'Vector-Best') followed by sequence identification of the rickettsial DNA detected. The DNA marker for Rickettsia species (a conservative area of citrate synthase gene, gltA) was detected in 16 of 84 (19.1%) samples of Rhipicephalus sanguineus ticks tested. Larger fragments of gltA, ompA and sca4 were amplified and sequenced for 10 of 16 PCR-positive samples. Rickettsia DNA amplified from eight of the samples matched the sequence of Rickettsia conorii conorii Malish, the causative agent of Mediterranean fever. The sequences of Rickettsia DNA from two other ticks had the closest match to homologous fragments of Rickettsia massiliae, a pathogenic spotted fever rickettsia that was identified in the Crimean Peninsula for the first time as part of this study. The detection of two pathogenic species of Rickettsia in the studied ticks suggests the potential for two rickettsial diseases in the region and warrants further epidemiological and clinical studies.

[The association of hemostasis system genes with the development of ischemic stroke in patients under the age of 50 years]. / Assotsiatsiia genov sistemy gemostaza s riskom razvitiia ishemicheskogo insul'ta u patsientov v vozraste do 50 let.

AIM: To study an influence of polymorphic variants of hemostasis system genes on the risk of ischemic stroke (IS) in patients of the Slavic population under the age of 50 years. MATERIAL AND METHODS: Ninety-two patients (19 women and 73 men), aged 18-50 years, were examined. The diagnosis of stroke was confirmed by neuroimaging (CT or MRI) in all patients. Polymorphic alleles of GP1BA, F2, F5 were studied by a real-time polymerase chain reaction using the TaqMan technology. RESULTS AND CONCLUSION: An analysis of the GP1BA -5T/C polymorphism showed that it was associated with IS in young men, lacunar stroke and stroke due to thrombosis of the brachiocephalic arteries. This association was not found in young women. The F5 G1691A polymorphism was associated with lacunar stroke. The F2 G20210A polymorphism was associated with stroke due to thrombosis of the brachiocephalic arteries.

Oxidant Potential of Krunidon In Vitro and In Vivo.

We studied the effect of Fe2+ ions in polymerized hemoglobin (Krunidon blood substitute) and in molecular hemoglobin (Sigma) on OH• radical initiation in the Fenton system. It was found that polymerized hemoglobin, as a component of Krunidon preparation, in contrast to hemoglobin tetramer, did not intensify OH• radical generation. The oxidant potential of Krunidon was evaluated in vivo by measuring malondialdehyde level in dog blood plasma after repeated intravenous administration (5 days in a dose of 114 mg/kg) as a biomarker. Administration of the preparation did not significantly increased malondialdehyde content on days 1 and 4 after exposure and did not affect total protein content in blood plasma. Our findings suggest that polymerized hemoglobin in the Krunidon preparation exhibits no pro-oxidant activity and can be used as the basis for the development of non-oxygenic forms of blood substitutes.

[The biomarkers of cerebral ischemia as a new method for the validation of the efficacy of cytoprotective therapy]. / Biomarkery ishemii golovnogo mozga kak novyi metod dokazatel'stva éffektivnosti neirotsitoprotektorov.

AIM: To study blood plasma concentrations of NR2-peptide in patients with ischemic stroke (IS) to assess its diagnostic value as a biomarker of cerebral ischemia and determine the dynamics of the biomarker during treatment with cortexin. MATERIAL AND METHODS: One hundred and twenty patients, aged from 18 to 70 years, including 36 with transient ischemic attack (TIA) and 84 with IS in the carotid territory (n=70) and vertebral/basilar territory with the Wallenberg-Zakharchenko syndrome (n=14), were enrolled. The National Institute of Health Stroke scale (NIHSS) was used to assess neurological status. Blood plasma concentration of NR2-peptide was measured in all patients at admission and after treatment. All laboratory results were compared with neuroimaging (MRI, CT) data. RESULTS: Concentrations of NR2-peptide detected in all patients were higher than in controls (>1.5 ng/ml), p<0.0001. The direct correlation between NR2-peptide (from 3.38 ng/ml to 15.6 ng/ml) and ischemic lesion (from few to 80 mm) was observed. A decrease in NR2-peptide concentration (from 8.5 to 5,.9 ng/ml, p<0.0001) was noted in patients treated with cortexin after 10-day treatment course. CONCLUSION: NR2-peptide blood assay is a reliable hemotest of brain ischemia. Cortexin has a sufficient therapeutic efficacy.

[A case of cutaneous protothecosis]. / Nablyudenie prototekoza kozhi.

The paper describes a case of a rare opportunistic infection, such as skin lesion caused by achlorophyllic unicellular algae of the genus Prototheca. It provides a detailed pathologic description of the foci of cutaneous protothecosis, such as pandermal inflammatory infiltrate, granulomas, pseudoepitheliomatous hyperplasia, and intraepidermal abscesses. Criteria for pathogen detection in histological sections are given.

Genetic Analysis of BDNF, GNB3, MTHFR, ACE and APOE Variants in Major and Recurrent Depressive Disorders in Russia.

This study was conducted to explore the possibility of association between the single-nucleotide polymorphisms rs6264 of BDNF, rs5443 of GNB3, and rs1801133 of MTHFR; the In/Del polymorphism of ACE; and the ε2 allele of APOE and major depressive disorder (MDD) and recurrent depressive disorder (RDD) in an East Slavic population. Generalized multifactor dimensionality reduction (GMDR) method was applied to detect gene-gene interactions. One hundred fifty patients with RDD (101 females and 49 males) and 208 patients with MDD (115 females and 93 males) were included in the study. The comparison group consisted of 200 unrelated individuals. There was no significant difference in genotype distributions or allele frequencies between the controls and any of the diagnostic groups. Nevertheless, the frequency of the G allele of rs1801133 of MTHFR was higher in the RDD group and the frequency of the C allele of rs6264 of BDNF was higher in the MDD group. The difference between the controls and specific disease groups almost reached statistical significance (P = 0.08). A GMDR did not reveal optimal two- and three-dimensional models with significant prediction accuracies (P ˃ 0.05) for the MDD or RDD groups.

Genetic variability of Rickettsia spp. in Ixodes persulcatus ticks from continental and island areas of the Russian Far East.

Rickettsia spp. are intracellular Gram-negative bacteria transmitted by arthropods. Two potentially pathogenic rickettsiae, Candidatus Rickettsia tarasevichiae and Rickettsia helvetica, have been found in unfed adult Ixodes persulcatus ticks. The aim of this study was to assess the prevalence and genetic variability of Rickettsia spp. in I. persulcatus ticks collected from different locations in the Russian Far East. In total, 604 adult I. persulcatus ticks collected from four sites in the Khabarovsk Territory (continental area) and one site in Sakhalin Island were examined for the presence of Rickettsia spp. by real-time PCR. Nested PCR with species-specific primers and sequencing were used for genotyping of revealed rickettsiae. The overall prevalence of Rickettsia spp. in ticks collected in different sites varied from 67.9 to 90.7%. However, the proportion of different Rickettsia species observed in ticks from Sakhalin Island significantly differed from that in ticks from the Khabarovsk Territory. In Sakhalin Island, R. helvetica prevailed in examined ticks, while Candidatus R. tarasevichiae was predominant in the Khabarovsk Territory. For gltA and ompB gene fragments, the sequences obtained for Candidatus R. tarasevichiae from all studied sites were identical to each other and to the known sequences of this species. According to sequence analysis of gltA, оmpB and sca4 genes, R. helvetica isolates from Sakhalin Island and the Khabarovsk Territory were identical to each other, but they differed from R. helvetica from other regions and from those found in other tick species. For the first time, DNA of pathogenic Rickettsia heilongjiangensis was detected in I. persulcatus ticks in two sites from the Khabarovsk Territory. The gltA, ompA and оmpB gene sequences of R. heilongjiangensis were identical to or had solitary mismatches with the corresponding sequences of R. heilongjiangensis found in other tick species.

[The role of computer and magnetic resonance imaging in patients with deafness]. / Rol' komp'yuternoi i magnitno-rezonansnoi tomografii u patsientov s glukhotoi.

The objective of the present study was to evaluate the potential of CT and MRI for diagnostics of congenital and acquired pathology of the inner ear in the deaf patients. Two groups of the patients were examined. The first group consisted of 75 patients with congenital or acquired deafness etiology. The second group was comprised of 75 patients with deafness associated with acute bacterial meningitis suffered in the preceding period. All the patients were examined by CT and MRI of temporal bones. The results of the study provided a basis for the development of indications for the application of CT and MRI to examine the patients presenting with hearing loss and deafness. CONCLUSION: CT and MRI make it possible to identify individual features of the temporal bone structure significant for the surgical treatment. MRI appears to have an advantage over CT for diagnostics of early obliteration of the cochlea. Both CT and MRI are the optional methods for the examination of the patients with deafness developing after meningitis.

Integrity of the dorsolateral periaqueductal grey is essential for the fight-or-flight response, but not the respiratory component of a defense reaction.

Periaqueductal grey is believed to be one of the key structures of the central respiratory stress network. Previous studies established that stimulation of the periaqueductal grey, especially its dorsolateral division (dlPAG), evokes tachypnea as well as increases in other autonomic parameters and motor activity. We investigated the effects of blockade of the dlPAG with GABAA agonist muscimol on respiration during stress and presentation of brief alerting stimuli in conscious unrestrained rats. We found that integrity of the dlPAG is not essential for stress-induced increase in basal/resting respiratory rate or for generation of respiratory responses to brief alerting stimuli. However, blockade of the dlPAG reduced the amount of motor activity and concomitant high-frequency respiratory activity during restraint and the first 5min of novelty stress. We conclude that the integrity of the dlPAG is not essential for generation of respiratory component of the defense reaction, but it mediates expression of the fight-or-flight response including its respiratory component.

[Results of Investigation of MRSA Susceptibility to Vancomycin in Clinical Units of Large Multifunctional Hospital and Recommendations on Optimization of Antibacterial Therapy of Staphylococcal Infection].

The frequency of MRSA and MRSE isolates in various units of the Voronezh Regional Hospital was investigated by the results of the local microbiological monitoring for 2014. The maximum position of MRSA was recorded in the ICU (38 to 75% of the strains). The MRSA strains were characterized by higher methicillin resistance, mainly from the cardiosurgical units (60 to 91% of the isolates). The use of the E-test for MRSA susceptibility to vancomycin allowed to estimate the validity of the use of various antibiotics active against MRSA in the treatment of inpatients and to reduce the risk of ineffective therapy.

[DNA detection of pathogens transmitted by Ixodid ticks in blood of small mammals inhabiting the forest biotopes in Middle Irtysh Area (Omsk Region, West Siberia)].

Microtine rodents were captured in two disconnected sampling sites in Omsk region where Ixodes pesulrcatus and Ixodes trianguliceps are sympatric. In blood samples of rodents the DNA was revealed belonging to several ixodid-transmitted pathogens: Borrelia burgdorferi sensu lato (prevalence 20.0 and 6.0%, here and further values are given for the first and second site, respectively), Borrelia miyamotoi (8.3 and 2.0%), Anlaplasnma phagocytophilum (33.3 and 48.0%), Ehrlichia muris (30.0 and 2.0%) and Babesia microti (33.3 and 42.0%). Three genetic groups of A. phagocytophilhm based on 16S rRNA gene and groESL operon, as well as two genetic groups of B. microti, B. microti 'US'-type and B. microti 'Munich'-type, were detected.

Prelimbic prefrontal cortex mediates respiratory responses to mild and potent prolonged, but not brief, stressors.

The prefrontal cortex is one of the key areas of the central mechanism of cardiovascular and respiratory control. Disinhibition of the prelimbic medial prefrontal cortex elicits tachypnoeic responses in anesthetized rats (Hassan et al., J. Physiol. 591: 6069-6088, 2013). The current study examines the effects of inhibition of the prelimbic prefrontal cortex during presentation of stressors of various lengths and intensities in conscious unrestrained rats. 8 Wistar rats were implanted with bilateral guide cannulas targeting the prelimbic prefrontal cortex and received microinjections of either saline of GABAA agonist muscimol prior to recording sessions. Inhibition of the prelimbic prefrontal cortex significantly attenuated respiratory responses to a novel environment stress, 30s light stimulus and restraint stress. It did not affect respiratory responses to 500 ms acoustic stimuli of varying intensities (40-90 dB). We conclude that the prelimbic prefrontal cortex contributes to generation of tachypnoeic responses to prolonged stressors, but does not contribute to respiratory arousal in response to brief stressors.