Casein, hydrolyzed casein, and amino acids that simulate casein produce the same extent of mucosal adaptation to massive bowel resection in adult rats.

We determined the effect of the extent of protein polymerization on the intestinal hyperplastic adaptation of adult male Wistar rats after 80% resection of the jejunal-ileal segment. Rats received one of four chemically defined solid diets prepared by using casein, two casein hydrolysates of different peptide size distributions, or free amino acids simulating casein and identical in all other components for 12 d, starting 3 d after surgery. Semipaired feeding was used to ensure that the same quantity of food was ingested by each group and as a consequence, nitrogen and energy intakes were reduced to 63% of that obtained with ad libitum feeding of the casein diet to intact rats. No significant differences were demonstrable in food ingestion, weight gain, nitrogen balance, or morphometric data for the remaining jejunal and ileal segments (number of cells/villus, number of cells/crypt, and crypt cell mitosis rate). These data demonstrate that the extent of polymerization of the protein nitrogen source did not affect the hyperplastic adaptative process of the rat. Additional studies in humans are necessary to determine whether intact protein diets can be used first as a nitrogen source in nutritional support of patients with a nonspecific hyperplastic response to surgical resection before the use of expensive hydrolysates and the more expensive amino acid mixtures.

Clonal analysis of colorectal tumors using K-ras and p53 gene mutations as markers.

Mutations to the K-ras oncogene and p53 tumor suppressor gene are two of the most common genetic lesions in human cancers. In the present study we examined the clonality of colorectal tumors with respect to each of these genetic alterations. Screening for mutations was carried out using the polymerase chain reaction-based technique of single-strand conformation polymorphism. Eleven primary colorectal adenocarcinomas and two secondary adenocarcinomas were analyzed at four different sites within the tumor. Involved pericolic lymph nodes were collected from nine of these cases, a metastatic deposit in the liver was obtained in one case, and adjacent adenomatous lesions were collected in two cases. Seven tumors contained mutations in either the K-ras or p53 genes. In all cases, DNA derived from multiple sites within an individual tumor or metastatic deposits arising from that tumor showed the same pattern of gene mutation. Immunohistochemical staining for p53 protein overexpression also showed similar patterns of reactivity within individual tumors and their metastatic deposits. These results suggest that the major clonal expansion of colorectal carcinomas occurs after the acquisition of mutations in these genes. Our results also indicate that sampling errors are unlikely to occur in molecular studies aimed at defining the role of these genes in colorectal cancer progression.

Amino acid patterns in the plasma and ascitic fluid of cirrhotic patients.

Amino acid levels were measured in the plasma and ascitic fluid of 13 alcoholic patients with liver cirrhosis and of 14 normal controls. The plasma aromatic amino acids of the alcoholic patients were not statistically different from those of the control subjects, whereas the levels of branched-chain amino acids were reduced (P less than 0.05). The values for the ratio of the muscle/liver metabolized amino acids (valine + isoleucine + leucine)/(phenylalanine + tyrosine + methionine) were statistically lower in the cirrhotic patients both in plasma and ascitic fluid (P less than 0.05). The amino acid levels in the ascitic fluid of the cirrhotic patients were slightly lower than those in the plasma of the same patients and the values for the muscle/liver metabolized amino acid ratio were similar in plasma and ascitic fluid. Aspartic acid, glutamic acid and glycine levels were higher among the cirrhotic patients (P less than 0.05). Cirrhotic patients present an alteration in amino acid metabolism which creates a different amino acid pattern in both plasma and ascitic fluid. The significance of the proposed ratio and its possible relation to hepatic failure are discussed.

[Peripheral lymphatico-venous anastomosis. New surgical technic]. / Anastomosi linfatico-venose periferiche. Nuova tecnica chirurgica.

A new surgical technique for peripheral lymphatic-venous anastomosis is presented. It is designed especially for cases of node block, e.g. lymphoedema after mastectomy. The distal ends of the collectors are sectioned downstream from the block and passed through a patch, which also serves to close a phlebotomy on an adjacent vein. An experimental study and preliminary clinical results are discussed.

[Changes in precordial movements in non-ischaemic heart disease patients after i.v. administration of isoproterenol and dopamine. Comparison between normal and cardiopathic subjects (author's transl)]. / Modificazioni dei movimenti precordiali in cardiopatici non ischemici durante l'infusione intravenosa di isoproterenolo e di dopamina. Considerazioni comparative con individui normali e coronaropatici.

18 patients with non-ischemic heart disease have been studied with reference to the kinetocardiographic changes before and after i.v. administration of dopamine (DOP) (Revivan) or Isoproterenol (ISP) (Aleudrin). For this purpose a simultaneous registration of ECG (lead D2), Kinetocardiogram (KCG) in K25 and K45 was performed. Volume curves were considered as a normal features of KCG, curves showing systolic outward movements during the ejection phase were classified as pathologic. The reduction or disappearance of the systolic movements during the drug administration, were considered as kinetic improvement, the increase of their site was judged as kinetic worsening. During the infusion, 17 KCGs maintained a normal morphological pattern; out of 19 pathological KCGs, 4 did not show any change, and 15, 5 reached a complete normalization. It is pointed out the overlap of the precordial kinetics in the ventricular hypertrophies and in the normal subjects (kinetic improvement), and the possibility to differentiate a systolic outward movement due to synergic contraction of hypertrophied ventricle from a systolic outward movement to be reffered to a diskynetic contraction in the myocardial ischemia (kinetic worsening).

Disorders in peripheral arterial system in asymptomatic elderly: plethysmographic semiology at rest, during postural, effort and pharmacological tests.

The vascular system of 30 old asymptomatic patients (average age 62.5 years) was studied by reflection plethysmography. The plethysmogram (PTG) was recorded from the forefinger of the left hand at rest, during two postural tests (+45 degrees arm-up and -45 degrees arm-down), after physical work, and during the infusion of nitroglycerin and the beta-agonist metaproterenol. 50% of the subjects presented a normal PTG under basal conditions. However, pathological PTGs were recorded after the various tests: 23.3% with the arm-up test, 6.6% with the arm-down test, 52% with the effort test, 31% with the nitroglycerin test and 73.9% with the metaproterenol test. Clearly, the effort and metaproterenol tests are pathological in the majority of cases, both tests inducing physiologically vasodilation and increase in the peripheral pulse. The arm-down test, which usually induces vasoconstriction, is almost always normal. Since the percentage of pathological responses to the nitroglycerin test is significantly smaller than that to the effort and metaproterenol tests, it is concluded that the vascular changes induced by aging are primarily functional, at least in asymptomatic subjects. Aging more negatively influences the vasodilating than the vasoconstricting ability.

The therapeutic value of clonidine in patients with coronary heart disease.

11 coronary patients, 8 with mild hypertension, were treated with clonidine, at a dose of 75 micrograms b.i.d. per os for a week. The effect of the drug on coronary heart disease was assessed by means of a symptom-limited multistage exercise test on the cycloergometer. Clonidine was effective in reducing the exercise-induced increases in blood pressure (by 15.5 +/- 6.1%), the double product (by 34.8 +/- 20.8%) and the electrocardiographic ischemic changes. In 2/4 patients, effort related ventricular extrasystoles were reduced by greater than 50% after clonidine. The drug worsened the anginal pain in 3 and relieved the pain in 3 patients. However, it reduced the exercise-induced ST-T segment downsloping in 7 patients. The tolerance was good, since only 3/11 patients reported slight dry mouth, sedation and pyrosis. In view of the electrocardiographic effect, further studies with clonidine on myocardial ischemia should be performed.

[Antiarrhythmic treatment with mexiletine in acute myocardial infarction (author's transl)]. / Trattamento antiaritmico con mexiletina nell'infarto acuto.

The effect of an introduced i.v. bolus of 250 mg of mexiletine was checked in cases of acute myocardial infarction with ventricular premature beats. On the 19 observed subjects 17 are male and 2 female: 18 cases with acute myocardial infarction and 1 with acute coronary failure. The introduction of the bolus was followed by an infusion of 0.75 mg/m for the successive four days. After 60 m' no significant changes in arterial pressure and in the heart rate were recorded. The Extrasistolies decrease from 11 +/- 3 to 3 +/- 2/m' (-71%, p less than 0.01); PQ and QT variations were not significant. After four days of infusion, systolic arterial pressure decrease from 135 +/- 4 to 121 +/- 3 (-10%; p less than 0.01), sinusal rate drops from 90 +/- 4 to 80 +/- 3 (-12%, p less than 0.05). The changes of diastolic arterial pressure, PQ and QT were not significant. Extrasistolies disappears entirely. A comparison between a mexiletine and a xilocaine i.v. bolus showed that mexiletine performs a higher antiarrhythmic activity.

Enzymatic inactivation of bradykinin by rat brain neuronal perikarya.

1. Bradykinin (Bk; Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg8) inactivation by bulk isolated neurons from rat brain is described. 2. Bk is rapidly inactivated by neuronal perikarya (4.2 +/- 0.6 fmol/min/cell body). 3. Sites of inactivating cleavages, determined by a kininase bioassay combined with a time-course Bk-product analysis, were the Phe5-Ser6, Pro7-Phe8, Gly4-Phe5, and Pro3-Gly4 peptide bonds. The cleavage of the Phe5-Ser6 bond inactivated Bk at least five fold faster than the other observed cleavages. 4. Inactivating peptidases were identified by the effect of inhibitors on Bk-product formation. The Phe5-Ser6 bond cleavage is attributed mainly to a calcium-activated thiol-endopeptidase, a predominantly soluble enzyme which did not behave as a metalloenzyme upon dialysis and was strongly inhibited by N-[1(R,S)-carboxy-2-phenylethyl]-Ala-Ala-Phe-p-aminobenzoate and endo-oligopeptidase A antiserum. Thus, neuronal perikarya thiol-endopeptidase seems to differ from endo-oligopeptidase A and endopeptidase 24.15. 5. Endopeptidase 24.11 cleaves Bk at the Gly4-Phe5 and, to a larger extent, at the Pro7-Phe8 bond. The latter bond is also cleaved by angiotensin-converting enzyme (ACE) and prolyl endopeptidase (PE). PE also hydrolyzes Bk at the Pro3-Gly4 bond. 6. Secondary processing of Bk inactivation products occurs by (1) a rapid cleavage of Ser6-Pro7-Phe8-Arg8 at the Pro7-Phe8 bond by endopeptidase 24.11, 3820ACE, and PE; (2) a bestatin-sensitive breakdown of Phe8-Arg9; and (3) conversion of Arg1-Pro7 to Arg1-Phe5, of Gly4-Arg9 to both Gly4-Pro7 and Ser6-Arg9, and of Phe5-Arg9 to Ser6-Arg9, Phe8-Arg9, and Ser6-Pro7, by unidentified peptidases. 7. A model for the enzymatic inactivation of bradykinin by rat brain neuronal perikarya is proposed.

Circadian variations of sinus rate in subjects with sinus node dysfunction.

Circadian variations of sinus rate (SR) are well described in subjects with normal sinus node (SN). On the other hand there are no data in literature concerning the SR daily variations in patients with SN dysfunction. In order to clarify this problem we studied the SR circadian variation in healthy subjects (12) and in patients with intermittent bradycardia (11), persistent bradycardia (9) and intermittent 2:1 sino-atrial block (7). Sr was recorded utilizing ECG Holter monitoring. By histograms obtained every 2 h, maximum, modal, and minimum SR were evaluated. Time series were analyzed with a computer program for cosinor method. In the patients with normal SN, circadian periodicity in SR was confirmed with acrophase at 16(26) (Maximum SR), 16(38) (minimum SR) and 16(31) (SR mode), respectively. In patients with intermittent bradycardia a circadian rhythm was detected only in minimum SR (Acrophase: 16(51)) and in SR mode (acrophase: 16(13)). No statistically significant circadian variations of the 3 parameters of SR were observed in patients with both persistent bradycardia and sino-atrial block. These data suggest that: 1. the disappearance of the circadian periodicity is proportional to the severity of SN dysfunction; 2. the patients with intermittent bradycardia show a more normal behavior at low rates than at high ones; 3. the disappearance of circadian rhythm in patients with marked SN dysfunction can be related to the SN intrinsic involvement and/or autonomic nervous system dysfunction.

[Value and limits of echocardiography of the acute or previous myocardial infarction. Mono- and bi-dimensional study (author's transl)]. / Valore e limiti dell'ecocardiografia nell'infarto miocardico acuto e pregresso. Studio mono e bidimensionale.

81 subjects with acute or previous myocardial infarction were studied in order to assess the relations between ecg location and diskinetic zones as seen on the echocardiogram; another purposes of the work was to establish if serial echocardiographic measurements would be useful for prognostic purposes. The obtained results were the following: 1) there is a good correlation between ecg location of anterior infarction and diskinetic or ipokinetic zones if on the echocardiographic pattern were simultaneously present the following echocardiographic findings: lessened systolic escursion + lessened systolic thickening + enhanced left ventricular diastolic dimension (LVDD); 2) in the group of posterior and inferior infarctions is observed either an ipokinetic left ventricular posterior wall either an ipokinetic septum; 3) left ventricle diastolic dimension (LVDD) was greater and the motion of the septum was less frequently paradoxical in previous infarction than in acute infarction; 4) there was a good correlation in anterior acute infarction among M-mode echo-patterns which indicate both progressive dilatation of the left ventricle and an abnormal septum movement and the appearance of congestive failure, shock and intrahospital mortality; 5) the aneurysms localized in apical section of the ventricles could be missed by M-mode studies and therefore when this complication is suspected bidimensional investigations are more indicated.

[Circadian variations of sinus rate in subjects with normal or pathological sinus node (author's transl)]. / Variazioni circadiane della frequenza sinusale in soggetti con nodo del seno normale e patologico.

Circadian variation of sinus rate (SR) is well described in subjects with normal sinus node (SN). On the other hand there are on data in literature concerning the SR daily variations in patients with SN disfunction. In order to clarify this problem we studied the SR circadian variation in normal subjects (12, and in patients with intermittent bradycardia (11), persistent bradycardia (9) and intermittent 2:1 seno-atrial block (7). SR was recorded utilizing ECG Holter monitoring. By histograms obtained every two hours, modal, maximum and minimum SR were evaluated. Time series were analyzed with a computer program for cosinor method. In the patients with normal SN, circadian periodicity in SR was confirmed with acrophase at 1626 (maximum SR), 1638 (minimum SR) and 1631 (SR mode), respectively. In patients with intermittent bradycardia a circadian rhythm was detected only in minimum SR (acrophase 1651) and in SR mode (acrophase: 1631). No statistically significant circadian variations of the 3 parameters of SR were observed in patients with both persistent bradycardia and sinoatrial block. These data suggest that: - the disappearance of circadian periodicity is proportional to the severity of SN dysfunction; - the patients with intermittent bradycardia show a more normal behavior at low rates than at high ones; - the disappearance of circadian rhythm in patients with marked SN disfunction can be related to SN intrinsic involvement and/or autonomic nervous system disfunction.

A heme-binding protein from hemolymph and oocytes of the blood-sucking insect, Rhodnius prolixus. Isolation and characterization.

A heme-binding protein has been isolated and characterized from both the hemolymph and oocytes of the blood-sucking insect, Rhodnius prolixus. The protein from both sources is identical in most aspects studied. The Rhodnius heme-binding protein (RHBP) is composed of a single 15-kDa polypeptide chain coiled in a highly alpha-helical structure which binds non-covalently one heme/polypeptide chain. This RHBP is not produced by limited degradation of hemoglobin from the vertebrate host, since specific polyclonal antibodies against it do not cross-react with rabbit hemoglobin, and since it differs from hemoglobin in having a distinct amino-acid composition and NH2-terminal sequence. The spectrum of the dithionite-reduced protein has peaks at 426, 530, and 559 nm and resembles that of a b-type cytochrome. RHBP from hemolymph is not saturated with heme and promptly binds heme added to the solution. The oocyte protein, on the other hand, is fully saturated and is not capable of binding additional heme.