Anatomical variations of the biceps brachii insertion: a proposal for a new classification.

BACKGROUND: The biceps brachii (BB) muscle is one of the three muscles located in the anterior compartment of the arm. Its insertion consists of two parts. The first part - main tendon - attached in the radial tuberosity and the second part - lacertus fibrosus (LF) - in the fascia of the forearm flexors. The intention of research was to reveal the morphological diversity of the insertion of this muscle. Thanks to the results of this work, have been created a classification of the distal attachment of BB. The results of that research can be used to further develop surgical procedures in the given region. MATERIALS AND METHODS: Eighty (40 left, and 40 right, 42 female, 38 male) upper limbs fixed in 10% formalin solution were examined. RESULTS: We observed three types of the insertion of the BB. Type I was characterised by a single tendon and occurred most frequently in 78.75% of the examined limbs. The second most common type was type II which was characterised by a double tendon and was observed in 13.75% of all the limbs. The last and least common was type III which was characterised by three tendons and occurred in 7.5% of the examined limbs. Additionally, the type of LF was analysed. In 8 (10%) specimens it was absent, i.e. in 2 specimens with type II insertion and 6 specimens with type III (p = 0.0001). Therefore, it may be deduced that type III BB insertion tendon predisposes to LF deficiency. CONCLUSIONS: The BB tendon is characterised by high morphological variability. The new classification proposes three types of distal attachment: type I - one tendon; type II - two separated band-shaped tendons; type III - three separated band-shaped tendons. The presence of type III BB tendon predisposes to a lack of LF.

The ulnar head of the pronator teres muscle originating from the third head of the biceps brachii: a very rare case.

The biceps brachii is located in the anterior compartment of the arm, which can show numerous morphological variations. During anatomical dissection, an interesting additional muscle was found: the third head of the biceps brachii originated from the short head of the same muscle. The 97.77 mm long muscle belly was directed medially over the arm and then passed into the common tendon (15.97 mm), which thereafter split into aponeurosis and tendon. The 26.33 mm aponeurosis passed and joined the fascia of the forearm. The tendon of the third head of the biceps brachii then gave rise to the ulnar head of the pronator teres muscle. Such an accessory structure could cause neurovascular compression involving the brachial artery and median nerve. Knowledge of the morphological variability of this region is essential not only for anatomists but also for clinicians.

Anatomical variation of co-existing bilaminar tensor of the vastus intermedius muscle and new type of sixth head of the quadriceps femoris.

BACKGROUND: We present a case report of quadriceps femoris (QF) with co-existing bilaminar tensor of the vastus intermedius (TVI) muscle and new type of sixth head. MATERIALS AND METHODS: Cadaveric dissection of left thigh of a 72-year-old man was performed for research and teaching purposes at the Department of Anatomical Dissection and Donation, Medical University of Lodz. The left lower limb was dissected using standard techniques according to a strictly specified protocol. Each head of the muscle was photographed and subjected to further measurement. RESULTS: During dissection, an unusual type of TVI muscle was observed. It consisted of two surfaces, superficial and deep. In addition, sixth head of QF muscle grew out from the vastus medialis muscle. CONCLUSIONS: The knowledge of the existence and possible variations of additional heads of QF muscle is necessary during diagnostic process of muscle strains. Moreover, according to course of tendons that heads may take part in patella stabilisation.

Potential compression of the musculocutaneous, median and ulnar nerves by a very rare variant of the coracobrachialis longus muscle.

The coracobrachialis longus muscle (CBL) is an extremely rare variant of the coracobrachialis muscle (CRM). The CBL originates from the apex of the coracoid process together with the short head of the biceps brachii and inserts on the olecranon of the ulna. The CBL consists of three parts: a superior part (classical CRM - length 137.88 mm), a middle fibrous layer (23.41 mm), and an inferior part (185.37 mm). A rare relationship between the CBL and median, musculocutaneous and ulnar nerves was observed with potential compression at these three parts. In addition, this case report describes a connection between CBL and the medial head of the triceps brachii, as well as a third head of the biceps brachii, which originate from the fibrous layer. This case report highlights the relationships between the CBL and the median, ulnar and musculocutaneous nerves.

Types of inferior phrenic arteries: a new point of view based on a cadaveric study.

BACKGROUND: The diaphragm is supplied by the superior and inferior phrenic arteries. This present study focusses on the latter. The inferior phrenic arteries (IPA) usually originate from the abdominal aorta. The two arteries have different origins, and knowledge of these is important when performing related surgical interventions and interventional radiological procedures. The aim of this study was to identify variations in the origin of the IPA and conduct relevant morphometric analyses. MATERIALS AND METHODS: The anatomical variations in the origins of the left inferior phrenic artery (LIPA) and the right inferior phrenic artery (RIPA) were examined in 48 cadavers fixed in 10% formalin solution. A dissection of the abdominal region of the cadavers was performed according to a pre-established protocol using traditional techniques. Morphometric measurements were then taken twice by two of the researchers. RESULTS: In the cadavers, six types of origin were observed. In type 1, the most common type, the RIPA and LIPA originate from the abdominal aorta (AA) (14 = 29.12%). In type 2, the RIPA and the LIPA originate from the coeliac trunk (CT) (12 = 24.96%). In type 3, the RIPA and the LIPA originate from the left gastric artery, with no CT observed (3 = 6.24%). Type 4 has two subtypes: 4A, in which the LIPA originates from the AA and the RIPA originates from the CT (9 = 18.72%) and 4B, in which the RIPA originates from the AA and the LIPA originates from the CT (6 = 12.48%). In type 5, the LIPA originates from the AA and the RIPA originates from the AA (1 = 2.08%). Type 6 is characterised by the RIPA and LIPA forming a common trunk originating from the CT (3 = 6.24%). CONCLUSIONS: Our findings suggest the presence of six different types of LIPA and RIPA origin. The most common form is type 1, characterised by an IPA originating from the abdominal aorta, while the second most common is type 2, in which the IPA originates from the AA by a common trunk. The diversity of other types of origin is associated with the occurrence of coeliac trunk variation (type 3). No significant differences in RIPA diameter could be found, whereas LIPA diameter could vary significantly. No significant differences in RIPA and the LIPA diameter could be found according to sex.

Anatomical variations of the abductor pollicis longus: a pilot study.

BACKGROUND: The abductor pollicis longus (APL) originates from the lateral part of the dorsal surface of the body of the ulna below the insertion of the anconeus muscle, from the interosseous membrane, and from the middle third of the dorsal surface of the body of the radius. However, the number of its accessory bands and their insertion vary considerably. MATERIALS AND METHODS: Fifty upper limbs (2 paired, 31 male, 19 female) were obtained from adult Caucasian cadavers, and fixed in 10% formalin solution before examination. RESULTS: The APL muscle was present in all specimens. The muscles were divided into three main categories, with type II and III being dived into subtypes. Type I was characterised by a single distal attachment, with the tendon inserting to the base of the I metacarpal bone. Type II was characterised by a bifurcated distal attachment, with the main tendon inserting to the base of the first metacarpal bone; this type was divided into three subtypes (a-c). Type III was characterised by the main tendons inserting to the base of the first metacarpal bone, while the accessory band was characterised by mergers (fusion) with other tendons. This type was divided into two subtypes (a, b). CONCLUSIONS: The abductor pollicis longus is characterised by high morphological variability.

Development of a recombinant NP protein based indirect ELISA for the detection of antibodies against Newcastle disease virus and differentiation of infected or recombinant vaccine immunized chickens.

Newcastle disease (ND) is a highly contagious and economically important disease in the poultry industry caused by avian avulavirus-1, historically known as Newcastle disease virus (NDV). Control of ND primarily relies on prophylactic vaccination of flocks, and many vaccines are available on the market, both conventional and more recently introduced new generation recombinant types. To assess the protection level achieved by vaccination ELISA tests are typically used, they also are to track an infection with field strains in non-vaccinated flocks. Special modifications of ELISA can be used as a screening tool to detect infection in flocks vaccinated with new generation vaccines. In this study, we have developed an ELISA test for the detection of antibodies against the nucleoprotein (NP) of NDV and for differentiation of chickens vaccinated with commercial and prototype in-house recombinant vector vaccines from those infected with field NDV strains. The NP gene of LaSota NDV strain expressed in a baculovirus vector was used as a coating antigen in the ELISA. The developed test was optimized, validated and compared to other serological tests. The sensitivity, specificity and accuracy of recombinant NP protein-based ELISA were respectively 96.1%, 96.3%, and 96.2%. Inter-rater (kappa) agreement between the NP-ELISA and the gold standard HI test was calculated to be 0.995. In our comparisons, commercially available ELISA tests revealed different specificities ranging from 95.5-100% and sensitivities at variance, ranging from 90.1 to 99.0%. A high level of maternally derived antibodies was measured in the serum of 1-day-old broilers in the NP-ELISA assay. These antibodies had disappeared and were undetected at 3, 5 and 6 weeks post-vaccination but birds became positive again at 2 weeks after control infection with a velogenic NDV strain. In SPF chickens, antibodies against NP protein were detected only after a challenge. The recombinant NP protein-based ELISA test is sensitive, specific and accurate when compared to the gold standard HI test and commercially available kits. Moreover, the method could be also used for the differentiation between vaccinated and infected birds.

The role of zinc deficiency-induced changes in the phospholipid-protein balance of blood serum in animal depression model by Raman, FTIR and UV-vis spectroscopy.

Depression is a serious mental illness. To study the mechanisms of diseases and search for new, more effective therapies, animal models are used. Unfortunately, none of the available models does reflect all symptoms of depression. Zinc deficiency is proposed as a new animal model of depression. However, it has not been yet validated in a detailed manner. Recently, spectroscopic techniques are increasingly being used both in clinical and preclinical studies. Here we examined the effect of zinc deficiency and amitryptyline treatment on the phospholipid - protein balance in the blood serum of rats using Raman, Fourier Transform Infra Red (FTIR) and UV-vis technique. Male Sprague Dawley rats were fed with a zinc ample diet (ZnA, 50mg Zn/kg) or a zinc deficient diet (ZnD, 3mg Zn/kg) for 4 weeks. Then amitriptyline administration (AMI, 10mg/kg, i.p.) was started. After injecting the drug for 2-weeks, blood samples were collected and analyzed. It was found that zinc deficiency decreases both the level of phospholipids and proteins and also causes structural changes in their structures. In the ZnD group amitriptyline treatment influenced the protein level and structure. UV-vis spectroscopy combined with the second derivative calculated from the FTIR spectra provided information that the proteins in blood serum of rat fed with a low Zn diet regain their intact structure after amitriptyline medication. Simultaneously, the antidepressant therapy did not have any effect on the level of phospholipids in this group of rats. Additionally, our results show, that amitriptyline administration can change the structure of phospholipids in rats subjected to zinc ample diet. This altered structure of phospholipids was identified as shortening of carbon chains. Our findings indicate that the decreased level of zinc may be the cause of depressive disorders, as it leads to changes in the phospholipid-protein balance necessary for the proper functioning of the body. This study also shows possible new applications of spectroscopic techniques in the diagnosis of affective disorders, and maybe even identifies markers of depressive disorders.

Preserved global histone H4 acetylation linked to ETV6-RUNX1 fusion and PAX5 deletions is associated with favorable outcome in pediatric B-cell progenitor acute lymphoblastic leukemia.

Epigenetic dysregulation is a hallmark of cancer executed by a number of complex processes the most important of which converge on DNA methylation and histone protein modifications. Epigenetic marks are potentially reversible and thus promising drug targets. In the setting of acute lymphoblastic leukemia (ALL) they have been associated with clinicopathological features including risk of relapse or molecular subgroups of the disease. Here, using immunocytochemistry of bone marrow smears from diagnosis, we studied global histone H4 acetylation, whose loss was previously linked to treatment failure in adults with ALL, in pediatric patients. We demonstrate that preserved global histone H4 acetylation is significantly associated with favorable outcome (RFS, EFS, OS) in children with B cell progenitor (BCP) ALL, recapitulating the findings from adult populations. Further, for the first time we demonstrate differential histone H4 acetylation in molecular subclasses of BCP-ALL including cases with ETV6-RUNX1 fusion gene or PAX5 deletion or deletions in genes linked to B cell development. We conclude global histone H4 acetylation is a prognostic marker and a potential therapeutic target in ALL.

Involvement of the monoaminergic system in the antidepressant-like activity of chromium chloride in the forced swim test.

Bio-metal chromium(III) is a crucial microelement for the proper functioning of living organisms. Previous preclinical and clinical studies reported its potential antidepressant properties. The aim of the present study was to examine the effect of antidepressants and noradrenergic and dopaminergic receptor antagonists on chromium chloride (CrCl3) activity in the forced swim test (FST) in mice and rats. Imipramine (5 mg/kg), fluoxetine (5 mg/kg) and reboxetine (5 mg/kg) but not bupropion (1 mg/kg), administered jointly with CrCl3 at a dose of 6 mg/kg, reduced the immobility time in the FST in mice. The reduction of the immobility time induced by the active dose (12 mg/kg) of CrCl3 was completely abolished by propranolol (2 mg/kg, ß-adrenoceptor antagonist), SCH 23390 (0.5 mg/kg, a dopamine D1 receptor antagonist), and partially by prazosin (1 mg/kg, an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, an α2-adrenoceptor antagonist) and sulpiryd (50 mg/kg, a dopamine D2/D3 receptor antagonist) administration. The locomotor activity was significantly reduced by CrCl3 + reboxetine treatment, which did not influence the reboxetine enhancement of the antidepressant-like effect of CrCl3 in the FST. Moreover, CrCl3 at a dose of 32 mg/kg (although not at 12 mg/kg) significantly reduced the immobility and enhanced the climbing (but not swimming) time in the FST in rats, which indicates the involvement of the noradrenergic pathway in this effect. The present study indicates that the antidepressant-like activity of chromium in the FST is dependent (although to a different extent) on the noradrenergic, dopaminergic and serotonin systems.

The involvement of NMDA and AMPA receptors in the mechanism of antidepressant-like action of zinc in the forced swim test.

Antidepressant-like activity of zinc in the forced swim test (FST) was demonstrated previously. Enhancement of such activity by joint administration of zinc and antidepressants was also shown. However, mechanisms involved in this activity have not yet been established. The present study examined the involvement of the NMDA and AMPA receptors in zinc activity in the FST in mice and rats. Additionally, the influence of zinc on both glutamate and aspartate release in the rat brain was also determined. Zinc-induced antidepressant-like activity in the FST in both mice and rats was antagonized by N-methyl-D-aspartic acid (NMDA, 75 mg/kg, i.p.) administration. Moreover, low and ineffective doses of NMDA antagonists (CGP 37849, L-701,324, D-cycloserine, and MK-801) administered together with ineffective doses of zinc exhibit a significant reduction of immobility time in the FST. Additionally, we have demonstrated the reduction of immobility time by AMPA receptor potentiator, CX 614. The antidepressant-like activity of both CX 614 and zinc in the FST was abolished by NBQX (an antagonist of AMPA receptor, 10 mg/kg, i.p.), while the combined treatment of sub-effective doses of zinc and CX 614 significantly reduces the immobility time in the FST. The present study also demonstrated that zinc administration potentiated a veratridine-evoked glutamate and aspartate release in the rat's prefrontal cortex and hippocampus. The present study further suggests the antidepressant properties of zinc and indicates the involvement of the NMDA and AMPA glutamatergic receptors in this activity.

Angiosarcoma in children - still uncontrollable oncological problem. The report of the Polish Paediatric Rare Tumours Study.

Angiosarcoma in children - still uncontrollable oncological problem. The report of the Polish Paediatric Rare Tumours StudyAngiosarcoma is a rare, highly malignant vascular neoplasm with little data available on its clinical course and management in children. Ten children with angiosarcoma (M/F: 6/4; aged 2, 3-16 years) registered in Polish Paediatric Rare Tumours and Soft Tissue Sarcomas Studies between 1992 and 2006. Primary tumour exceeded 5 cm in seven patients and affected mainly deep tissues (heart-2, head/neck, bladder, brain, liver and upper limb - one patient each). Four patients had regional and two metastatic diseases (lungs and bones). Three patients were initially misdiagnosed as haemangioma. Complete primary excision was unfeasible even in local stages. All patients received supplementing chemotherapy with no response in four. Radiotherapy was given to five children, including three after relapse. Three of five secondary tumour resections proved complete. Seven patients experienced relapses (mainly metastatic) and two continuous progression. Relapsed patients received chemotherapy +/- radiotherapy and surgery (three). Nine patients died of disease (overall survival 6-66 months), and one child after mutilating secondary resection is alive. Angiosarcoma in children is highly aggressive with an extremely poor prognosis. Complete primary excision is unfeasible, even in seemingly local stages. The response to chemotherapy is poor and the large number of metastatic recurrences suggests a need for systemic therapy modifications.

Formation of Pseudorabies virus glycoprotein E/I complex in baculovirus recombinant system.

Glycoproteins E (gE) and I (gI) of Pseudorabies virus (PRV) form a non-covalently bound complex to which a number of functions have been attributed. The gE/gI complex formation was studied using a series of full-length and truncated forms of gE and gI expressed in baculovirus recombinant system. Both glycoproteins were truncated by stepwise removal of their C-terminal parts and their ability to form the complex was studied by radioimmunoprecipitation. It was found that N-terminal domains of gE and gI containing first 122 and 106 aa, respectively, were sufficient for the complex formation.

Antidepressant-like activity of CGP 36742 and CGP 51176, selective GABAB receptor antagonists, in rodents.

BACKGROUND AND PURPOSE: A crucial role for the GABAB receptor in depression was proposed several years ago, but there are limited data to support this proposition. Therefore we decided to investigate the antidepressant-like activity of the selective GABAB receptor antagonists CGP 36742 and CGP 51176, and a selective agonist CGP 44532 in models of depression in rats and mice. EXPERIMENTAL APPROACH: Effects of CGP 36742 and CGP 51176 as well as the agonist CGP 44532 were assessed in the forced swim test in mice. Both antagonists were also investigated in an olfactory bulbectomy (OB) model of depression in rats, while CGP 51176 was also investigated in the chronic mild stress (CMS) rat model of depression. The density of GABAB receptors in the mouse hippocampus after chronic administration of CGP 51176 was also investigated. KEY RESULTS: The GABAB receptor antagonists CGP 36742 and CGP 51176 exhibited antidepressant-like activity in the forced swim test in mice. The GABAB receptor agonist CGP 44532 was not effective in this test, however, it counteracted the antidepressant-like effects of CGP 51176. The antagonists CGP 36742 and CGP 51176 were effective in an OB model of depression in rats. CGP 51176 was also effective in the CMS rat model of depression. Administration of CGP 51176 increased the density of GABAB receptors in the mouse hippocampus. CONCLUSIONS AND IMPLICATIONS: These data suggest that selective GABAB receptor antagonists may be useful in treatment of depression, and support an important role for GABA-ergic transmission in this disorder.

Remaining problems and controversies in the management of childhood head and neck soft tissue sarcomas: Retrospective (national) Multicenter Study of the Polish Pediatric Solid Tumors Group.

Soft tissue sarcomas in children are a heterogeneous group of malignant diseases. Among these, tumors localized in the head and neck region are especially difficult to treat. While multidisciplinary care has dramatically improved the prognosis of sarcoma patients, their treatment remains uncertain because of demand on radical surgical resection of the tumor. Achieving cure without deforming or mutilating the child remains the primary goal of treatment. This study is the multicenter (nationwide, 11 Polish centers) retrospective analysis of the treatment results in children having soft tissue sarcoma in the head and neck region during the previous decade (from 1991 to 2001). Late effects of the treatment are documented in long-term survivals. Eighty-five children from 1 to 212 months of age were included. Different multimodal treatment protocols were utilized (CWS-91, SIOP-MMT-91, and CWS-96). The median observation time was 25 months. Data on long-term effects were collected in 34 long-term survivals. Complete remission was achieved in 68 (80%) patients. Primary treatment failure occurred in 13 (15.3%) patients, all of whom succumbed in disease progression. Relapse occurred in 21 (30.9%) patients primarily achieving complete remission. Second primary neoplasm occurred in 3 children. The estimated 5-year event-free survival and the 5-year total survival rates for the whole group are 0.38 and 0.55, respectively. The main late effect documented in long-term survivals were cosmetic defects in 12 (35.3%) and visual field deficit or blindness in 8 (26.5%). Despite substantial improvement of the prognosis of pediatric soft tissue sarcomas, the multimodal treatment of head and neck region tumors remains controversial. Improved long-term outcome and focusing on psychosocial difficulties raise the important and difficult problem of functional results and cosmesis. Tumors localized in the orbit carry an excellent prognosis. However, the main late sequela is vision impairment and cosmetic defect due to the therapy given many years earlier. Two other tumor localizations--the parameningeal and nonparameningeal ones--still have bad prognosis. The observations made in this study confirm that main prognostic factors are the size of the primary tumor and the tumor stage. The worst prognosis remains invasive tumor (T2-stage) with a size over 5 cm. Individually adjusted multimodal therapy, which imperatively needs to be radical, though not mutilating, might minimize the late effects. Psychosocial problems in long-term survivors need to be focused on at the national level and better support must be provided in the future, involving a team of different medical and paramedical profiles.

Group III mGlu receptor agonists produce anxiolytic- and antidepressant-like effects after central administration in rats.

It was well established that compounds which decrease glutamatergic transmission via blockade of NMDA or group I mGlu receptors produce anxiolytic- and antidepressant-like action in animal tests and models. Since group III metabotropic glutamate receptor (mGluR) agonists are known to reduce glutamatergic neurotransmission by the inhibition of glutamate release, we decided to investigate potential anxiolytic- and/or antidepressant-like effects of group III mGluR agonists, after central administration in rats. It was found that group III mGluR agonists, (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-I) and 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (HomoAMPA), given intrahippocampally, produced a dose-dependent anxiolytic-like effect in the conflict drinking test. The effects of ACPT-I and HomoAMPA were reversed by (RS)-alpha-cyclopropyl-4-phosphonophenyl glycine (CPPG), group III mGluR antagonist. Moreover, a dose-dependent antidepressant-like action of group III mGluR agonists, ACPT-I and (RS)-4-phosphonophenylglycine (RS-PPG), but not HomoAMPA, was found in behavioral despair test, after intracerebroventricular injections, and the effect of ACPT-I was reversed by CPPG. The results obtained indicate that group III mGluR agonists produce anxiolytic- as well as antidepressant-like effects in behavioral tests, after central administration in rats. The reduction of glutamate release by group III mGluR activation may be a possible mechanism underlying anxiolytic- and antidepressant-like properties of the tested compounds. In conclusion, the results of our studies indicate that group III mGlu receptor agonists may play a role in the therapy of both anxiety and depression.

Characterization of changes in the short unique segment of pseudorabies virus BUK-TK900 (Suivac A) vaccine strain.

Mutant strains of pseudorabies virus (PRV) of reduced virulence, such as Bartha or BUK-TK900, have been used for vaccination purposes for many years. In contrast to the Bartha strain, BUK-TK900 has not been well characterised at the molecular level. The detailed analysis of this vaccine strain was urged by the fact of the isolation in Poland of field strains which were suspected to originate from BUK-TK900. We characterised changes in the U(S) region of this strain, focusing our attention on gE and gI genes. The only deletion, about 300 bp, found in BamHI 7 fragment (covering most of the U(S) region) was located in the 28 K (US2) gene. BUK-TK 900 produced small plaques on all cell lines tested in our laboratory (SK6, Vero, MDBK, 3T3). The plaque size was restored to about 70% of wild type virus plaque size when growing BUK-TK900 virus on 3T3 complementing cell line expressing PRV gE and up to 100% when cell line producing gE and gI was used. Both gE and gI genes from BUK-TK900 and from some derivative field isolates have been amplified by PCR reaction but no deletions in these genes have been found. Molecular weight of gene products differed from wild type proteins: gE was bigger than wild type gE while gI was smaller. Both proteins were correctly recognised by all tested polyclonal and monoclonal antibodies. Radioimmunoprecipitation study showed that BUK-TK900 gE and gI interact forming a complex. The whole ORF of BUK-TK900 gE was sequenced and only few point mutations were found; only two of them led to changes of amino acids in the polypeptide chain. These were: methionine at position 124 replaced by threonine and glutamine at position 162 replaced by arginine. The introduction of first of these mutations (Met to Thr) to PRV wild type strain NIA-3 resulted in 22% reduction of plaque size. This result confirms the importance of this domain of gE for its function; it was found previously by others that deletion of amino acids 125 and 126 reduced virulence and neurotropism of PRV. More changes were found in BUK-TK900 gI sequence. Over 80% of these changes were located in the terminal 1/3rd of the sequence. Some of these mutations may have significant effect on the secondary structure of gI glycoprotein. The change of the secondary structure may be responsible for the decrease of gI stability and the observed reduction of gI molecular mass.

Antidepressant-like effect of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist in the olfactory bulbectomized rats.

Using the olfactory bulbectomy model of depression, we examined the antidepressant-like activity of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) in rats. Bulbectomized rats required a significantly greater number of trials to acquire the response similar to sham-operated controls in the passive avoidance model. Both the prolonged (but not acute) treatment with MPEP and with antidepressant drug-desipramine restored the learning deficit. The results indicate that the prolonged blockade of mGlu5 receptors exerts antidepressant-like effects in rats.

Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats.

Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of action of anxiolytic and antidepressant drugs. The involvement of group I mGlu receptors in anxiety and depression has also been proposed. In view of the recent discovery of anxiolytic- or antidepressant-like effects of acute injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective and brain penetrable mGlu5 receptor antagonist, we designed the present study to examine anxiolytic- and/or antidepressant-like effects of multiple administrations of this drug. The anxiolytic-like effects of MPEP were evaluated in rats using the conflict drinking test. The antidepressant-like effect was estimated using the rat olfactory bulbectomy model of depression. Seven subsequent injections of MPEP (1 mg/kg) significantly (by 320%) increased the number of shocks accepted during the experimental session in the Vogel test. MPEP given once daily at a dose of 10 mg/kg, restored the learning deficit of bulbectomized rats after 14 days of treatment, remaining without any effect in the sham-operated animals. N-methyl-D-aspartic acid (NMDA)-induced convulsions in mice were not affected by a single injection of MPEP (30 mg/kg) indicating that at this dose MPEP did not block NMDA receptors. The results indicate that the prolonged blockade of mGlu5 receptors exerts anxiolytic- and antidepressant-like effects in rats. No tolerance to anxiolytic-like action occurs. The previously mentioned results further indicate that antagonists of group I mGlu receptors may play a role in the therapy of both anxiety and depression.

Effect of chronic imipramine or electroconvulsive shock on the expression of mGluR1a and mGluR5a immunoreactivity in rat brain hippocampus.

Previous studies showed that chronic electroconvulsive shock (ECS) or imipramine treatment induced a subsensitivity of group I metabotropic glutamate receptors (mGluR) in hippocampus. In the present study effects of antidepressant treatment on the expression of mGluR1a and mGluR5a, belonging to the group I mGluR, were investigated in rat brain hippocampus using immunohistochemical and Western blot methods, respectively. Male Wistar rats were treated singly or chronically for 21 days with imipramine, 10 mg/kg, twice daily; with ECS (90 mA, 50 Hz, 0.5 s) every second day; or with haloperidol, 1.2 mg/kg, once daily. Appropriate controls were injected with saline. Rats were sacrificed 24 h after the last treatment and their hippocampi were taken out for analysis. It was found that the mGluR1a-immunoreactivity expression increased significantly in Ammon's horn (CA) regions after chronic ECS. The most pronounced effect was observed in the CA3. No significant effects were found after single treatment or after haloperidol. The expression of mGluR5a increased significantly after chronic imipramine in the CA1 and after chronic ECS in the CA3 region. The results obtained indicate an influence of antidepressant treatment on group I mGluR. This increase in the receptor protein level may be a compensatory mechanism developing after chronic treatment.