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To investigate the protective role of high dose melatonin concerning myocardial I/R injury and inflammation in patients undergoing on-pump coronary artery bypass grafting (CABG) surgery by evaluating IR/inflammatory biomarkers and clinical outcomes. This was a prospective; randomized; single-blinded placebo-controlled study conducted at cardio-thoracic surgery department of the Academy of the Cardiovascular and Thoracic Surgery, Ain Shams University. Eligible patients were randomly allocated to; melatonin-treated group (MTG) or placebo-treated group (PTG). The MTG (n = 17) received 60 mg/day melatonin capsules daily starting 5 days before surgery in addition to the standard of care. PTG (n = 17) received placebo also 5 days before surgery plus standard of care. The levels of nuclear factor kappa beta (NF-κb) (primary outcome), tumor necrosis factor (TNF-α), cardiac troponins I, and IL-6 levels were all assessed for both groups at five time points: baseline before melatonin or placebo administration (T0), before cross-clamp application(T1), 5 min after cross-clamp removal(T2), 6 h after cross-clamp removal(T3) and 24 h after cross-clamp removal(T4). Blood pressure was assessed at baseline, pre-operative and 24-hours post-operative. The Quality of recovery-40 score (QOR-40) was assessed for both groups on day 4 after surgery. TNF-α levels decreased in the MTG at T1(p = 0.034) versus PTG. At T2(p = 0.005), and T3(p = 0.04), TNF-α significantly increased in PTG versus MTG. Troponins significantly increased in PTG at T3 (p = 0.04) versus MTG. NF-κB levels declined at T1 (p = 0.013) and T2 (p = 0.0001) in MTG compared to PTG. IL-6 significantly increased in PTG versus MTG at T3 (p = 0.04). The QOR-40 score significantly decreased in MTG versus PTG. MTG had statistically significant decrease in DBP compared to the placebo group (p = 0.024). MTG had a statistically significant shorter intubation time than did the placebo group (p = 0.03). Melatonin 60 mg was well-tolerated without any reported side effects. Our findings suggested that melatonin could ameliorate myocardial I/R injury after on-pump CABG and that this outcome was essentially correlated to its antiapoptotic and anti-inflammatory effects. Trial registration: ClinicalTrials.gov registration number NCT05552586, 9/2022., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted according to the Good Clinical Practice guidelines and followed the ethical principles in the Declaration of Helsinki (as revised in 2013). This study also applied the CONSORT guidelines and the ICMJE recommendations. The protocol was revised and approved by the committee of ethics for experimental and clinical studies at both the Faculty of Pharmacy and Faculty of Medicine, Ain Shams University, Cairo, Egypt. ClinicalTrials.gov registration number: NCT05552586. All participants were given information sheets explaining all the details pertaining to the study. Informed consents were obtained from all patients before their inclusion in the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Acute coronary syndrome (ACS) is one of the leading causes of mortality worldwide and negatively impacts healthcare costs, productivity and quality of life. Polymorbidity and polypharmacy predispose ACS patients to medication discrepancies between cardiologist-prescribed medication and drug use by the patient, drug-related problems (DRPs) and inadequate drug adherence. This study aimed to evaluate the impact of clinical pharmacist-provided services on the outcome of ACS patients. This was a prospective, randomized, controlled study on ACS patients participating in a cardiac rehabilitation programme. Forty ACS patients were randomly assigned to either control group, who received standard medical care, or intervention group, who received standard medical care plus clinical pharmacist-provided services. Services included DRP management, clinical assessment and enforcing the patient education and adherence. For both groups, the following were assessed at baseline and after 3 months: DRPs, adherence (assessed by 8-item Morisky Adherence Questionnaire), patient's knowledge (assessed by Coronary Artery Disease Questionnaire), 36-Short Form Health Survey (SF-36), heart rate, systolic and diastolic blood pressure, low-density lipoprotein (LDL), total cholesterol (TC) and fasting blood glucose (FBG). After 3 months, there was a significant difference between the intervention and control groups in the per cent change of DRPs (median: -100 vs 5.882, P = 0.0001), patient's adherence score (median: 39.13 vs -14.58, P = 0.0001), knowledge score (median: 30.28 vs -5.196, P = 0.0001), SF-36 scores, heart rate (mean: -10.04 vs 6.791, P = 0.0001), diastolic blood pressure (mean: -17.87 vs 10.45, P = 0.0001), systolic blood pressure (mean: -16.22 vs 4.751, P = 0.0001), LDL (median: -25.73 vs -0.2538, P = 0.0071), TC (median: -14.62 vs 4.123, P = 0.0005) and FBG (median: -11.42 vs 5.422, P = 0.0098). Clinical pharmacists can play an important role as part of a cardiac rehabilitation team through patient education and interventions to minimize DRPs., (© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Adult Dermacentor andersoni ticks were collected by flagging vegetation in 18 canyons bordering the Bitterroot Valley, Montana, an area where nearly 400 cases of Rocky Mountain spotted fever (RMSF) have occurred since 1900. Three hundred and nine (8.3%) of the 3,705 ticks collected contained hemocyte-associated rickettsia-like organisms of three morphologic types, coccobacillary, fine bacillary, and coarse bacillary (long forms). Only the coccobacillary and fine bacillary organisms stained with fluorescein-conjugated antibody specific for the spotted fever group. One hundred and six isolates of spotted fever-group rickettsiae obtained by inoculation of Vero cells with suspensions of hemolymph test-positive ticks were serologically typed by microimmunofluorescence. Four sharply distinct serotypes were obtained, including Rickettsia rickettsii (10 strains), R. montana (8 strains), R. rhipicephali (47 strains), and a hitherto undescribed serotype referred to as 369-C (41 strains). All but two isolates were obtained from west-side canyons where virtually all cases of RMSF had been acquired. The four serotypes were widely distributed on the west side as evidenced by their presence in 5-11 of the 13 collecting sites. Each serotype induced distinctive plaques and cytopathogenicity in Vero cell culture.

A rickettsial survey of ixodid ticks known to bite man was conducted in 1979 in four coastal counties of California to obtain isolates from tick species that might be involved in the transmission of spotted fever-like illnesses, and to examine serologic characteristics of the rickettsiae relative to defined members of the spotted fever group (SFG). One hundred and seventy (19.4%) of 877 ticks comprising three species were shown by hemolymph test to harbor rickettsia-like organisms. A total of 85 SFG rickettsia isolates was obtained by Vero-cell culture; 82 were from Dermacentor occidentalis, two were from D. variabilis, and one was from Ixodes pacificus. As determined by microimmunofluorescence, the isolates comprised four distinct serotypes. Two serotypes were obtained only from D. occidentalis, and one each only from D. variabilis and I. pacificus, respectively. Most D. occidentalis isolates possessed the serologic characteristics of Rickettsia rhipicephali, but there were similar to yet distinguishable from, R. rickettsii and are members of an unclassified serotype referred to as 364D. The two isolates from D. variabilis resembled the unclassified 369C serotype previously shown to be associated with this species and D. andersoni elsewhere in the United States. The I. pacificus isolate was similar to strains of the unclassified Tillamook serotype isolated from this tick in several localities in western Oregon. Representative strains of the four serotypes could also be distinguished on the basis of pathogenicity for Vero cells, chick embryos, guinea pigs, and/or meadow voles. The significance of these findings relative to occurrence of tick-associated illnesses in western California is briefly discussed.

A strain of Rickettsia canada was recovered in 1980 an adult rabbit tick, Haemaphysalis leporispalustris, taken from a black-tailed jack rabbit, Lepus californicus, in Mendocino County, California. In all examined biologic characteristics, this isolate, CA410, is indistinguishable from the prototype, strain 2678, isolated in Ontario, Canada, in 1963. These similarities include serologic and immunologic reactivity in laboratory mice and guinea pigs, cultural characteristics in Vero cells, chick embryo cells and embryonated eggs, low pathogenicity for mice, meadow voles and guinea pigs, unusual resistance to streptomycin, morphology by electron microscopy, and molar percentages of guanine plus cytosine of the deoxyribonucleic acids. Recovery of this second strain in the same species of tick, but far removed in time and place from the origin of the prototype, provides evidence that R. canada is an established, ecologically stable, rickettsia in North America.

Antibody production in humans and three species of laboratory animals infected with Rickettsia rickettsii was determined with the indirect hemagglutination test. Rabbits, guinea pigs, and mice were inoculated with R. rickettsii and bled at intervals. Antibody which agglutinated both fresh and glutaraldehyde-fixed sheep erythrocytes sensitized with antigen prepared either from purified rickettsiae or from infected yolk sacs was found in rabbit sera at all intervals tested (10 to 59 days postinfection). Antibody which agglutinated fresh but not glutaraldehyde-fixed erythrocytes sensitized with either of the above antigens was detected in guinea pig sera obtained 7, 14, and 28 days postinfection. Antibody was found in mice inoculated with 5.6 x 10(6) plaque-forming units of R. rickettsii but not in mice given 5.6 x 10(2) plaque-forming units. Peak indirect hemagglutination titers occurred in nonvaccinated human Rocky Mountain spotted fever patients about 3 weeks after onset of illness, and antibody was still detectable after 1 year. Both human immunoglobulin G and human immunoglobulin M antibodies agglutinated sensitized cells, but immunoglobulin M antibodies apparently were more efficient. The indirect hemagglutination test is useful for the titration of human, rabbit, guinea pig, and mouse antibodies when the appropriate erythrocytes are used.

Sera referred to the North Carolina Division of Health Services for rickettsial serology in 1974 were tested by complement fixation (CF), microimmunofluorescence (micro-IF), microagglutination (MA) and hemagglutination (HA) for antibodies against Rickettsia rickettsii. There was good agreement among micro-IF,MA and HA tests in detecting antibody responses to this agent, but the CF test was definitely less sensitive than the others, even in illnesses with classical clinical manifestations of Rocky Mountain spotted fever (RMSF). Some variables that seemed to influence the CF result were the slow rate of increase in antibody titers, timing of serum collection, early antibiotic treatment and possibly, the particular association of CF antibody response with the IgG immunoliobulin class. Greater use of these newer, but relatively untried, serodiagnostic procedures is recommended infuture studies of RMSF.

Only 4.2% of 284 single specimens and 17.6% of 51 pairs of sera reactive in Weil-Felix agglutination tests for Rocky Mountain spotted fever were confirmed by a specific Rickettsia rickettsii microimmunofluorescence test.

Rhipicephalus simus Koch was removed from a human upon his return to Connecticut, U.S.A. from Kenya, Africa. This person became ill in Africa, exhibited clinical manifestations of boutonneuse fever and had a significant rise (greater than or equal to 8-fold) in IgM titer against spotted fever-group rickettsiae. Rickettsia conorii was probably the infectious agent.

A microimmunofluorescence test was used to study antibody responses to various spotted fever group and typhus group rickettsiae during Rocky Mountain spotted fever (RMSF) and epidemic typhus (ET). Patients with RMSF reacted most strongly to Rickettsia rickettsii; those with ET reacted predominantly to R. prowazekii. The degree of cross-reaction to other rickettsial strains varied from patient to patient, but a particular pattern of cross-reaction was consistently observed in serial sera from the same patient. Fresh isolates from three Montana RMSF cases were indistinguishable from each other and from strain R of R. rickettsii used as a standard antigen in all tests. Immunoglobulin M (IgM) antibodies were usually present in high titer in early-convalescent-phase sera from RMSF, as well as ET, patients. After RMSF, IgM antibodies persisted for a few months and, in one instance, for as long as 10 months. IgM responses to laboratory-acquired infections were infrequent in persons previously vaccinated with antigens related to the infecting strain. Previous antigenic conditioning from infection or vaccination may have accounted partly for the apparent lack of IgM response in a few study participants.

To compare rickettsial infectivity and seropositivity rates against spotted fever group (SFG) rickettsiae, ticks and wild mammals were collected from three areas where Rickettsia rickettsii was thought to be enzootic in Connecticut during 1978-1979, and from four additional sites (with no reported human cases) between 1976 and 1979. Of the 1,001 Dermacentor variabilis examined by the hemolymph test, 59 (5.9%) contained rickettsia-like organisms; direct immunofluorescence tests verified the presence of SFT rickettsiae in 14 specimens. Prevalence of rickettsiae-infected ticks at Newtown, an area where human cases of Rocky Mountain spotted fever probably originated, was 2.2%. Rates for six other areas ranged between 0 and 6.3%. Isolations included Rickettsia montana from four ticks collected at Branford and Woodbridge, and R. rickettsii (R-like strain) from the blood of an acutely ill person. Microagglutination (MA) tests indicated that 15 (14.9%) of 101 Peromyscus leucopus (white-footed mice) from Newtown had agglutinins in titers greater than or equal to 1:8 against R. rickettsii, whereas five of 92 white-footed mice (5.4%) from Brandord, West Hartford, Woodbridge, and Sharon were considered MA-positive. Indirect microimmunofluorescence tests of Procyon lotor (raccoon) sera revealed antibodies to R. rickettsii in 33 of 69 (47.8%) samples from Newtown and in two of 60 (3.3%) from Guilford. Additionally, 17 raccoons had sera specific to R. montana (n = 8) or to the 369-C rickettsia strain (n = 9). Since rickettsia-positive ticks are high-titered seropositive mammals occurred at widely separated sites in Connecticut there are probably several foci of SFG rickettsiae distributed throughout the D. variabilis range.