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Hydroxapatite and tricalcium phosphate prepared by precipitation method.

A mixture with different compositions of HA and TCP were synthesize in this work by precipitation method using Ca(NO3)2 4H2 and (NH4)2HPO4 as the starting materials. A mixture with HA and TCP phases in different ratios were produced. The powders were sintered from 1000 degrees C to 1250 degrees C. The phase compositions of the mixtures were then studied via XRD. This work shows that the pH value determines the different phase compositions of the HA-TCP mixture. Chemical analyses were carried out by FTIR. The microstructure was observed under SEM.

Biocompatible Materials↗

[An experimental study on repairing bone defect with composite of beta-tricalcium phosphate-hyaluronic acid-type I collagen-marrow stromal cells].

OBJECTIVE: To observe the ability to repair bilateral radius bone defect with the composite of beta-tricalcium phosphate (PTCP), hyaluronic acid (HA), type I collagen (COL-I) and induced marrow stromal cells (MSCs), and to investigate the feasibility of the composite as a bone substitute material. METHODS: The MSCs of the New Zealand white rabbits were induced into osteoblasts, then combined with beta-TCP, HA and COL-I. Thirty New Zealand white rabbits were made the bilateral radius bone defects of 2 cm and divided into groups A, B and C. After 8 weeks, beta-TCP-HA-COL-I-MSCs (group A, n=27 sides), autograft (group B, n=27 sides)and no implant (group C as control, n=6 sides) were implanted into the areas of bilateral radius bone defects, respectively. The structure of the composite was observed by scanning electron microscope. The repairing effect was observed by gross, histomorphology, X-ray examination, and the degradation rate of inorganic substance at 4, 8 and 12 weeks. The osteogenic area and biomechanics of group A were compared with those of group B at 12 weeks. RESULTS: The MSCs could stably grow in vitro, relatively rapidly proliferated, and could be induced into the osteoblasts. The composite was porous. The results of gross, histomorphology and X-ray showed that the bone defects were perfectly repaired in group A and group B, but not in group C. The osteogenic area or biomechanics had no statistically significant difference between groups A and B (P> 0.05). The weight of inorganic substance in group A were 75%, 57% and 42% at 4, 8, 12 weeks, respectively. CONCLUSION: MSCs can be used as seed cells in the bone tissue engineering. The composite has porous structure, no reactions of toxicity to the tissue and rapid degradation, and it is an ideal carrier of seed cells. The beta-TCP-HA-COL-I-MSCs composite has the high ability of repairing bone defect and can serve as an autograft substitute material.

Animals↗

[Effects of the recombinant plasmid carrying the genes of cholera prophages CTX and RS1 on the expression of virulence and immunogenicity genes in the cholera pathogen].

Using toxin-coregulated adhesion pili (TCP), the etiologic agent of cholera is able to colonize human small intestine, where this pathogen proceeds with the production of the secreted cholera toxin (CT), inducing the development of severe diarrhea. At the same time, TCP and CT are not only the major factors of pathogenicity but also form a part of the group of key protective antigens. Immunoenzyme, immunoblotting, self-agglutination investigations, electron-microscopic studies, and electrophoretic assay of the outer membrane proteins showed that the recombinant plasmid carrying a number of cloned genes of two prophages, CTX and RS1, introduced into model Vibrio cholerae strains classical biovariant, resulted in the formation of strains with an enhanced rate of synthesis of three protective antigens: CT, TCP, and an outer membrane protein, OmpU. A simultaneous increase in the level of biosynthesis of the three antigens in V. cholerae was demonstrated to be specified by alterations in the expression of the toxR regulatory gene. Information was obtained suggesting that the transcriptional activity of toxR gene was dependent on the activity of rstC antirepressor gene derived from RS1 pro-phage and localized in the cloned fragment. Strains hyperproducing the three protective antigens can be used to construct more efficient non-living cholera vaccines, and to isolate the indicated proteins applicable to the development of diagnostic test-systems.

Adhesins, Bacterial↗

[Reconstruction of dentin-pulp complex structure by tissue engineering technology].

OBJECTIVE: To investigate the possibility of reconstruction of dentin-pulp complex by tissue engineering technology. METHODS: Rat dental pulp stem cells were seeded into HA-TCP scaffold and incubated for 20 hours in vitro. Then the cell-scaffold complex was implanted subcutaneously into the dorsal side of nude mice. 8 weeks postimplantation, the samples were extracted for histological and immunohistochemical examinations. RESULTS: Three strata of tissue were observed in the hole of HA-TCP scaffold. They were dentin-like tissue, predentin-like tissue and pulp-like tissue respectively from the inner surface of the pore to the center. Dentin tubules were obvious in predentin-like and dentin-like tissue lining from the pulp-like tissue through predentin-like tissue and dentin-like tissue. Cells localized along the edge of pulp-like tissue were dense and polarized, resembling odontoblasts. Immunohistochemical study demonstrated DSP and DMP1 expression in these odontoblast-like cells and in the area of predentin-like tissue. CONCLUSIONS: Tissue-engineered rat dentin-pulp complex was reconstructed by seeding HA-TCP scaffold with rat dental pulp stem cells.

Animals↗

[Impact of PET/CT on precise radiotherapy planning for non-small cell lung cancer].

OBJECTIVE: To investigate the impact of PET/CT on the clinical staging, target volume delineation and precise radiotherapy (PAR) planning for patients with non-small cell lung cancer (NSCLC). METHODS: PET/CT scanning was performed in 58 histologically proven NSCLC patients for radical radiotherapy or surgery. The clinical staging of all patients was determined by PET/CT according to 1997 World Health Organization (WHO) staging system. The gross tumor volume (GTV) was delineated and three-dimensional conformal radiotherapy (3D-CRT) planning was established with identical parameters based on CT image and PET/CT fused image, respectively. The indexes including volume of GTV (V(GTV)), percentage of the total lung volume which received more than 20 Gy (V(20)), mean lung dose (MLD), tumor control probability (TCP), normal tissue complication probability (NTCP), and dose to spinal cord (Ds) were selected and evaluated. The quality of the two plans and the impact of PET/CT on PAR planning was compare and analyzed. RESULTS: 1. PET/CT image results changed the clinical stages in 21 of 58 (36.2%) patients with 14 upstaged and 7 downstaged, therefore, the management decisions were modified in 16 (27.6%) patients. 2. Among 32 patients who underwent surgery, PET/CT staging result was consistent with pathologic staging in 29 with one false negative and 2 false positive in lymph node staging. The sensitivity of PET/CT was 96.9% and accuracy 90.6%. 3. The differences of indexes including V(GTV) (P = 0.004), V(20) (P = 0.000) and MLD (P = 0.004) between the two radiotherapy plannings were statistically significant, whereas, the Ds, TCP and NTCP (left lung, right lung, skin and spinal cord) was not. CONCLUSION: 1. The impact PET/CT on clinical staging of NSCLC and PAR planning was remarkable. 2. PET/CT is more consistent with pathology in staging than CT and, therefore, is an important compensatory staging measure. 3. Compared with CT, PET/CT can reduce the V(GTV) in patients with atelectasis and obstructive pneumonitis when contouring the target volume, so can provide better protection for normal surrounding lung tissue. On the other hand, PET/CT is more sensitive in detecting mediastinal lymph node metastasis than CT, and the V(GTV) can be more precise and guaranteed. 4. Radiopneumonitis may be more effectively prevented because of significant decrease in V(20) and MLD by more precise planning based on PET/CT results. 5. PET/CT not only can provide satisfactory Ds, TCP and NTCP within clinical demand, but also more precise delineation of the radiation target volume and precise radiotherapy planning for NSCLC.

Adult↗

Antithrombotic effect of MCI-9042, a new antiplatelet agent on experimental thrombosis models.

The antithrombotic effect of MCI-9042, (+-)-2-(dimethyl-amino)-1-((o-(m- methoxyphenethyl)phenoxyl]methyl]ethyl hydrogen succinate hydrochloride was investigated in three different experimental thrombosis models in animals. Simultaneous injection of serotonin and collagen into the tail vein in mice induced acute pulmonary thromboembolic death. MCI-9042 reduced the mortality in a dose dependent manner and its ED50 value was 1.9 mg/kg po. Ticlopidine (TCP) which is a positive reference compound as an antithrombotic drug reduced the mortality at doses of 10 mg/kg po and above. Cyproheptadine (CPH) and ketanserin (KTS) which are S2-serotonergic antagonists were also effective on the reduction of mortality. In mesenteric arterial thrombosis induced by electric stimulation in mice, MCI-9042 prolonged the occlusion time resulted from platelet thrombus formation (PD50: 23 mg/kg po). CPH and KTS prolonged the occlusion time as potent as MCI-9042, but TCP prolonged the occlusion time only at the high doses of 100 mg/kg po and above. In experimental arterial thrombosis which generated in implanted polyethylene tubing, MCI-9042 reduced the incidence of thrombus formation in the tubing and its ED50 value was 18 mg/kg po. TCP was also effective in this model with an ED50 of 170 mg/kg po. The present results lead to the consideration that serotonin plays a more important role in thrombus formation than that conjectured formerly, and suggest that MCI-9042 becomes a new kind of antithrombotic drug with S2-serotonergic receptor antagonism.

Animals↗

[Treatment of periodontal infrabony defects with alloplastic implantation materials].

The implantation of alloplastic materials in infrabony defects is controversely discussed. Only calcium phosphate ceramics have been proven as implantation materials for clinical use. All of the materials not being inert they undergo biodegradation. The extent of biodegradation is most pronounced with tricalciumphosphate (TCP). It had been shown in clinical studies that reduction of probing depth and gain of probing attachment level increased with implantation when compared to surgery only. Formation of new attachment however, can only be verified by histological analysis. Block sections of human teeth demonstrated different results in terms of gain of attachment when porous hydroxyapatite (HA) was implanted. Histometric analysis of a study in dogs showed significant gain of attachment by implanting porous HA and TCP in infrabony defects. Using solid HA or a modified Widman flap healing occurred only by reparation forming a long junctional epithelium. In conclusion, it can be stated that regeneration of periodontal tissues may be achieved by means of implantation of porous HA and TCP. However, long term results are not available and the clinical parameters to obtain predictable results still have to be defined.

Alveolar Bone Loss↗

Calcium phosphate cements: study of the beta-tricalcium phosphate--dicalcium phosphate--calcite cements.

The setting and strengthening properties of beta-tricalcium phosphate (beta-TCP)--dicalcium phosphate dihydrate (DCPD)--calcite blends upon admixture with water were investigated at 25 and 37 degrees C. Setting was accelerated by seeding the system with hydroxyapatite (HAp), and strengthening improved when the solids were mixed with a solution saturated with DCPD and HAp. The relationship strength versus ageing time in wet conditions was correlated with mineralogical changes of the material. X-Ray diffraction, thermal analysis and scanning electron microscopy observations showed that DCPD and calcite react together to form small HAp crystals acting as bridges between the beta-TCP aggregates present in the paste. Both gaseous CO2 released by the reaction of calcite and the conversion of lower (DCPD, calcite) to higher-density phases (HAp) contributed to increase the porosity of the material. Nevertheless, quite acceptable diametral strengths (around 1.5 MPa) could be achieved, despite the high porosity of the hardened product (up to 54 vol%). After exhaustion of DCPD, calcite can react with beta-TCP to form further HAp, but this process is detrimental to the strength of the material. Both the mineralogical transformations, and the strengthening of the material were accelerated considerably upon increasing the ageing temperature.

Adhesives↗

[Prolonged inflammatory reactions induced by ceramic powders in the rat air pouch model].

The subcutaneous air pouch of the male Sprague-Dawley rat was used to study inflammatory potential of artificial ceramics. Local leukocyte influx, proteinase, prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) levels were measured after injection of hydroxyapatite ceramic (HAP), tricalcium phosphate ceramic (TCP) and apatite-wollastonite glass ceramic (GC) into the pouch. Synthetic monosodium urate crystals (MSU) were used as positive controls and normal saline (NS) as a negative control. The response was monitored over a period of 168 hours by irrigating the pouch with 5 ml of NS and withdrawing 4 ml. MSU produced the greatest response in leukocyte counts, proteinase and PGE2, whereas HAP, TCP and GC often appeared later than with MSU. TNF was significantly detected only after ceramics and not after MSU. The chronic and relatively prolonged reaction to HAP, TCP and GC suggests that an inflammatory reaction may occur after implantation of these ceramics in humans. The increased levels of TNF and production of PGE2, which are substances proposed to contribute to osteolysis associated with loosening, are of special interest for further research.

Animals↗

Faecal chymotrypsin assay in tropical and alcoholic chronic pancreatitis.

Faecal chymotrypsin (FCT) levels were estimated in a group of patients with tropical chronic pancreatitis (TCP) and compared with patients with alcoholic chronic pancreatitis (ACP), 'gastrointestinal' controls and 'healthy' subjects. Exocrine pancreatic insufficiency as assessed by low faecal chymotrypsin levels (less than 5.8 mu/g) were present in 85.7 per cent of TPC and 84.6 per cent of ACP patients. Mean FCT levels as well as the distribution of FCT values were similar in TCP and ACP patients and significantly lower than the two control groups (P less than 0.001). There was also no difference with respect to mean FCT levels between subgroups of TCP patients with and without diabetes and those with and without calcification. Faecal chymotrypsin assay is a simple test for diagnosis of chronic pancreatitis in gastroenterological centres in tropical countries.

Alcoholism↗

[Effect of stress on the cardiomyocyte transmembrane potential of the working heart and its recovery after hypothermia].

Emotional-painful stress in rats was shown to decrease insignificantly transmembrane cardiomyocyte potential (TCP) measured in isolated hearts. The recovery of TCP following its depression due to the preparation cooling was twice slower in stress-exposed than in control animals. This is in keeping with the data on stress-induced disturbances of Na, K-ATPase activity (an enzyme playing a leading role in TCP maintenance). It is suggested that the disturbance in cation pump function activity plays a certain role in the onset of arrhythmias and cardiac fibrillation during stress.

Animals↗

[Excitotoxic damage of the hippocampus in the rat: involvement of N-methyl-D-aspartate receptors].

The intrahippocampal injection of two agonists of excitatory aminoacid (EAA) receptors elicited neuronal damages localized in CA1 and dentate gyrus for N-methyl-D-aspartate (NMDA) (20 nmol) and extended to the various hippocampal areas, except dentate gyrus for kainic acid (KA) (2.5 nmol). The pretreatment of the animals with N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) (20 mg/kg), a noncompetitive NMDA-receptor antagonist, prevented the neuronal injury induced by NMDA and KA in CA1. The distribution of neuronal damages and of TCP-protected areas closely correlated to that of EEA-receptors and of TCP binding sites in the hippocampus.

Animals↗

Tricyclic antidepressants and dextromethorphan bind with higher affinity to the phencyclidine receptor in the absence of magnesium and L-glutamate.

Recent studies from our laboratory have provided evidence that multiple states of the phencyclidine (PCP) receptor exist. In addition, several compounds such as PCP and the novel anticonvulsant MK-801 were found to inhibit binding more potently in the presence of Mg2+ and L-glutamate (L-GLU) than when these agents were excluded from the binding assay. In the present study, a number of pharmacological compounds that have been suggested to interact within the N-methyl-D-aspartate (NMDA) receptor complex, including tricyclic antidepressants (TCAs), were examined for their ability to inhibit the binding of [3H]1-[1-(2-thienyl)cyclohexyl]piperidine [( 3H]TCP) in the absence or presence of Mg2+ and L-GLU. The TCAs imipramine, amitriptyline, and opipramol produced shallow inhibition curves in the absence of Mg2+ and L-GLU. Computer analysis of the binding data indicated that a two-component binding model described the data significantly better than a one-component model. In the presence of Mg2+ and L-GLU, the inhibition curves became steeper and were shifted to the right, and computer analysis of the binding data indicated that a one-component model adequately described the binding data. A series of other centrally active compounds, including several antipsychotics and antihistamines, the antiparkinsonian anticholinergic trihexyphenidyl and the antitussive dextromethorphan, were also found to be affected similarly by the inclusion of Mg2+ and L-GLU in the binding assay. Dextrorphan, in contrast to dextromethorphan, inhibited [3H]TCP binding more potently in the presence of Mg2+ and L-GLU. The present results suggest that the compounds that inhibit binding more potently in the absence of Mg2+ and L-GLU are interacting with the PCP receptor in a different manner from that of PCP and MK-801, because these open-channel blockers inhibit [3H]TCP binding more potently in the presence of Mg2+ and L-GLU. The data support previous findings that TCAs interact with the NMDA receptor complex and suggest that the compounds trihexyphenidyl and dextromethorphan, which have been shown to block NMDA-mediated neurotoxicity, may produce their effects through an interaction with the PCP receptor, albeit by a different mechanism from that of open-channel blockers.

Animals↗

Characterization of opioid, sigma, and phencyclidine receptors in the neuroblastoma-brain hybrid cell line NCB-20.

Opioid, sigma, and phencyclidine (PCP) receptors were characterized in the mouse neuroblastoma--Chinese hamster brain hybrid cell line NCB-20. Quantitative receptor assays under equilibrium binding conditions with highly specific radioligands demonstrated the presence of delta, but not mu or kappa, opioid receptors on NCB-20 cell membranes. NCB-20 cells were shown to possess two distinct sites specific for sigma opioids and PCP derivatives. One site was labeled by (+)-[3H]N-allylnormetazocine [(+)-[3H]SKF-10,047] (Kd = 69 nM; Bmax = 4100 fmol/mg of protein). The rank order of potency of drugs at this site was (+)-3-(3-hydroxy-phenyl)-N-(1-propyl)piperidine [(+)-3-PPP] greater than haloperidol greater than (+)-SKF-10,047 greater than (+/-)-ethylketocyclazocine greater than (+/-)-bremazocine greater than N-[1-(2-thienyl) cyclohexyl]piperidine (TCP) greater than dexoxadrol. This site is similar in its ligand selectivity to the haloperidol-sensitive sigma receptor of rat brain. The other site was labeled by the potent phencyclidine derivative [3H]TCP (Kd = 335 nM; Bmax = 9300 fmol/mg of protein). This density is equivalent to approximately 60,000 sites/cell. The rank order of potency of drugs at this site was TCP greater than (+)-3-PPP greater than PCP greater than dexoxadrol greater than haloperidol greater than cyclazocine greater than levoxadrol greater than (+)-SKF-10,047; mu and delta ligands were inactive. This site is similar to the rat brain PCP receptor. The NCB-20 cell line is the only cultured cell line that has been demonstrated to have PCP receptors.

Animals↗

Initial identification and characterization of sigma receptors on human peripheral blood leukocytes.

Phencyclidine (PCP) has been reported to suppress a variety of immune functions in vitro. Because PCP binds with high affinity to both PCP and sigma receptors, the identity of the receptor(s) mediating the immunological effects of PCP is unknown. The aim of the present study was to identify and characterize the sites of PCP action (sigma and/or PCP receptors) in human peripheral blood leukocytes (PBL) using [3H]haloperidol or 1,3 di(2-([5-3H]tolyl)guanidine ([3H]DTG) to specifically label sigma receptors and 3,4-[3H]-(N)-[1-(2-thienyl)-cyclohexyl]-piperidine ([3H]TCP) to specifically label PCP receptors. [3H]Haloperidol binding was saturable and of high affinity with comparable KD values in human PBL (0.44 +/- 0.10 nM) and rat cerebellum (0.51 +/- 0.09 nM). Similarly, [3H]DTG binding was saturable with comparable KD values of 29.5 +/- 3.5 and 26.4 +/- 3.6 nM in rat cerebellum and human PBL, respectively. In contrast, there was a notable absence of [3H]TCP-labeled PCP receptors in human PBL and rat cerebellum. In competition studies, the pharmacologic profile of [3H]haloperidol-labeled sigma receptors in human PBL was virtually identical with that in rat cerebellum (slope, 0.87; correlation coefficient, 0.96); the rank order of potency of competing drugs was haloperidol greater than l-butaclamol = pentazocine greater than d-3-(hydroxyphenyl)-N-(1-propyl)-piperidine greater than DTG = d-butaclamol = d-SKF 10,047 greater than levallorphan greater than or equal to PCP greater than or equal to l-SKF 10,047 greater than TCP greater than MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A study of the biological characteristics of a hybrid line between male Schistosoma haematobium (Dar es Salaam, Tanzania) and female S. intercalatum (Edea, Cameroun).

The viability of a hybrid between male Schistosoma haematobium (Dar es Salaam, Tanzania) and female S. intercalatum (Edea, Cameroun) was studied for up to the F7 hybrid generation and the biological characteristics of the hybrid were compared with those of each of the parental species. Using the total cercarial production/100 exposed snails/5 weeks value (TCP) as an index the hybrid miracidial infectivity to Bulinus forskalii (Kinshasa, Zaire), the host snail for S. intercalatum, remained comparable to that of S. intercalatum for up to at least the F5 generation and the TCP values for the hybrid/B. wrighti combination remained for up to the F7 generation intermediate between those of the parental species in B. wrighti. The hybrid also retained the infectivity for up to at least the F5 generation to B. globosus (Mazeras, Kenya), the host snail for S. haematobium, but the TCP values for the hybrid/B. globosus combination remained consistently lower than that of the S. haematobium/B. globosus combination. The hybrid cercarial infectivity to hamsters was for up to the F7 generation comparable to that of both parental species and the egg production capacity/worm pair/day of production of the F1 hybrid generation exceeded in both hamsters and mice that of both parental species. However, the egg production capacity subsequently decreased with that of the F3 to F6 generations in hamsters and with that of the F2 and F5 generations in mice being comparable to that of S. intercalatum. The pattern of distribution of eggs in tissue of hamsters of the F1 and F2 generations resembled that of S. haematobium and S. intercalatum, respectively, but the distributional pattern of the F3 to F6 generations deviated markedly from that of both the parental species and the preceding hybrid generations. The hybrid cercarial infectivity to mice and the pattern of egg distribution corresponded to that of S. intercalatum. The egg morphology of the P1 generation corresponded to that of S. intercalatum while that of the F1, F2 and F3 hybrid generations exhibited great polymorphism with a range of shapes through those of the parental species but with most eggs being intermediate in shape. However, the eggs of the F4 to F7 hybrid generations exhibited less polymorphism and resembled those of S. bovis in both size and shape.

Animals↗

Prolonged inflammatory reactions induced by artificial ceramics in the rat air pouch model.

The male Sprague-Dawley rat subcutaneous air pouch was used to study the inflammatory potential of artificial ceramics that are used in joint replacement surgery. Local leukocyte influx, proteinase, prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) levels were measured after injection of hydroxyapatite type I ceramic (HAP), tricalcium phosphate ceramic (TCP) and apatite-wollastonite glass ceramic (GC) into the pouch. Synthetic monosodium urate crystals (MSU) were used as positive controls and normal saline (NS) was a negative control. The response was monitored over 168 h by irrigating the pouch with 5 ml of NS and withdrawing 4 ml. MSU produced the greatest response in leukocyte counts, proteinase and PGE2, whereas HAP, TCP and GC elicited less response. The peak response with HAP, TCP and GC often appeared later than with MSU. TNF activity was significantly detected only after ceramics and not after MSU. The chronic and relatively prolonged reaction to some ceramics suggests that an inflammatory reaction may be seen after human implantation of these ceramics. The increased levels of TNF and production of PGE2, which is one substance proposed to contribute to bone lysis associated with loosening, are of special interest.

Air↗

Oral tyramine pressor test and the safety of monoamine oxidase inhibitor drugs: comparison of brofaromine and tranylcypromine in healthy subjects.

The pressor effect of orally administered tyramine (TYR) has been evaluated in 124 tests of 49 healthy unmedicated volunteers, in 99 tests of 29 subjects treated with the reversible selective monoamine oxidase (MAO) A inhibitor brofaromine (BROF), and in 73 tests of 12 subjects treated with tranylcypromine (TCP). In unmedicated subjects, pressor doses of TYR to raise systolic blood pressure (BP) by 30 mm Hg (PD30) ranged between 200 and 800 mg of TYR. There was no correlation of PD30 with sex, age, or weight. In repeated tests, the intraindividual coefficient of variation of the PD30 (+/- SD) was 10 +/- 9%. During treatment for 8 to 16 days with the two MAO inhibitors (MAOIs) BROF and TCP, seven-fold and 56-fold increases of TYR pressor sensitivity were estimated. A significant correlation was found between the individual PD30 before and during MAO inhibition with BROF. Cheese with a pressor content equal to the PD30 of TYR raised the systolic BP in only three of 10 volunteers during BROF inconsistently by not more than 20 mm. Therefore, the probability of "cheese reactions" during treatment with this reversible MAOI seems to be small. For complete normalization of oral pressor responsiveness, delays of 8 and 30 days after the last doses of BROF and TCP, respectively, are needed. The total incidence of systolic BP elevations by more than 60 mm Hg was 13% in a total of 296 oral tests given to 49 subjects. This incidence of easily controllable hypertensive reactions is outweighed by the importance of the test as predictor of clinical risks for drugs with TYR potentiating effects.

Adolescent↗