As I near the completion of two print projects, I have to begin considering ePub creation. I haven't created ePubs since my last project, over a year ago, so I have to check my tools and revisit the process.
ePub Tools
I use Word 2003 to convert my Word document to Web Page Filtered htm segments. Each segment is the equivalent of a Chapter, example: Title Page, Copyright Page, Introduction (if included), Foreword (if included), Dedication (if included), Interior Chapters and Sections (all segmented), About the Author (if included), etc.
Anthemion Jutoh 2.93.2 (x86/x64) Multilingual 82.6 Mb Jutoh makes it easy to create ebooks in popular formats that you can sell on many ebook sites. Create your project in seconds from existing files using the New Project Wizard; or create your book from scratch using the built-in styled text editor. Anthemion Software Jutoh 2.93 (macOS / Linux) 193 MB Easily create ebooks in Epub and Kindle formats: publish on any ebook distribution site, including Amazon's Kindle, Apple's iBooks, Google Play, Kobo, and more. Your readers can use Kindles, iPads, iPhones, Android tablets. For information about migrating from Jutoh 2 to Jutoh 3, please see the FAQ. Jutoh for Windows. Jutoh supports Windows XP, Vista, 7, 8, and 10. Windows 8/10 users: click on More info when you get the 'Windows protected your PC' screen, and then click Run anyway in the next screen. Jutoh provides many tools to help, including the Inspector tool, Find and Replace, Document Cleanup, support for footnotes, tables of contents, indexes and bibliographies, and much more. Check Launch your book in appropriate viewers such as Kindle Previewer 3 and Adobe Digital Editions.
Jutoh
Afterward, I import the htm segments into Jutoh http://jutoh.com/, my ePub creator/editor. One project is already in an older version of Jutoh (1.75) while the other project will be imported into a new version (2.11). The new version handles fixed layout ePubs and that's perfect for the math book that has lots of rows of numbers that I don't want to flow from one page to another. I haven't had good results with creating Kindle and iBook eBooks in Jutoh's old version but I'll try to with the new.
Calibre
I've used Calibre http://calibre-ebook.com/ to convert my Jutoh created ePubs to Kindle and iBook compatibility with good results. Caliber is constantly updated so I check regularly to make sure my version is up to date before I begin my conversions.
https://dpbrzn.over-blog.com/2021/01/winrar-on-iphone.html. Book Cover Pro
I use Book Cover Pro http://www.bookcoverpro.com/ to create my print and eBook covers but I alsouse a very handy small commercial graphics tool called IrfanView http://www.irfanview.com/ to quickly and easily size my covers precisely to pixels, cm or inches. Precision is important because in order to get a properly printed cover, it has to match the size requested by the printer.
Photoshop
Although there are two great free graphic tools (GIMP http://www.gimp.org/ and Inkscape http://www.inkscape.org/en/), suitable for use by pros and novices, I use Photoshop with Action plug-ins to create 3-D images of my book covers for the web. Examples can be seen at: http://www.indpublisher.com/Pages/default.aspx https://cooljfil470.weebly.com/free-casino-coins.html.
RH
I became interested in Calibre after reading about it on an ePub creator/reader review page. That was a few years back and it was listed as an ePub reader/converter. At the time I was still looking for a free or low cost ePub creator. Also reviewed on the page was Sigil an ePub editor. I downloaded and installed both. I was able to create great ePubs in Sigil but all seemed to have errors when checked with the Validator. I imported them into Calibre and converted them to Mobi for Kindle. Even when I was able to create an error free ePub with Sigil, it would be rejected by the ePub vendors. I was able to create Mobi for Kindle with Calibre that was accepted. Later I switched to Jutoh http://jutoh.com/ to create my ePubs.
How I use Calibre
My intended primary use of Calibre was as an eReader and second to convert ePubs to Mobi (Kindle). At the time I was using Sigil, a free ePub creator/editor, to create my ePubs and afterward imported them into Calibre to convert to Mobi. I didn't, yet, have a Kindle so I had to preview the Mobis in the Kindle for PC Reader. Calibre can be configured to preview Mobis within Calibre using the Open With selection. Other programs such as Jutoh and Sigil can be opened within Calibre using Open With. Although I can use this method to edit an already created ePub in Calibre using its creator, I don't. To avoid the possibility of errors, I preview the entire ePub, shutdown Calibre, edit the ePub in its creator program, delete the old ePub and import the new, then preview it again. After purchasing a Kindle, I use Calibre to transfer the newly created Mobi to it for digital proofing. I only use the ePub to Mobi conversion but there are a few others like, AZW3, HTMLZ, LIT, PDF, TXT, etc. If you're interested in trying Calibre go here http://calibre-ebook.com/. You can download and try Calibre or read the User Manual in the Help section. It's a free program with regular updates.
RH
I use Jutoh exclusively for creating and editing my ePubs because it's low cost, easy to use and produces error free results…if I stick to protocol.
Jutoh, the beginning
About three books in the past, I was seriously searching for a low cost way to convert my two books to ePub. There were a number of third party ePub converters but I wanted to convert them myself. I was reading reviews, on a website, of software that self-publishers could use to create and edit ePubs and ironically, there was one that I had sitting idle on my computer, eCub by Anthemion. It was free but the company also had a more robust commercial ePub creator/editor called Jutoh http://jutoh.com/ and it was low cost, $39.00. I mention the price here because it has more than paid for itself by enabling me to produce ePubs for a variety of vendors, LuLu, Google, Barnes and Noble, iBooks and creating ePubs that could be converted to the Kindle format (mobi) using Calibre.
Using Jutoh
When I first began looking for an ePub creator/editor; I wanted a program similar to one that could convert a Word doc to PDF with one click and I found some but the results were far from suitable. The more I looked, the more I found suggestions that the best error free ePubs were built manually. I had always considered 'building manually' meaning using a program like Notepad or Notepad++, writing in Notepad or importing the text, converting the text to htm and importing the htm to an ePub creator/editor or using Notepad or Notepad++ to compile the htm into an ePub. Jutoh made the ePub process easier. It's still a manual build but easy. I began by copying and pasting each print-ready Word doc into a Jutoh folder. I do this because the print-ready Word doc is already edited and proofread. I then convert each segment to htm and the htms are imported into Jutoh. The segments are assembled to match the print-ready layout (title page, copyright page, foreword, dedication, chapters, etc). After the htms are assembled, edited and proofread, I run the Compiler, then run the Error Checker to check for errors and if there are none, preview the newly created ePub in Adobe Digital Editions. To create an ePub that meets iBooks requirements, I select the 'Optimize for iBooks' configuration. Although Jutoh can optimize for Mobi (Kindle), I don't use it because I get better results using Calibre to convert my ePubs to Mobi. Using Jutoh, I can import a book cover or create one. I can also edit ePubs and make layout adjustments, such as text, type, size and color, justification, spacing, indents, etc. If you're interested in learning more about Jutoh, you can download this free book titled Creating Great Ebooks Using Jutoh, here http://jutoh.com/book.htm.
RH
Mechanism of Action
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. The precise mechanisms by which amlodipine relieves angina have not been fully delineated, but are thought to include the following:
Exertional Angina: In patients with exertional angina, amlodipine reduces the total peripheral resistance (afterload) against which the heart works and reduces the rate pressure product, and thus myocardial oxygen demand, at any given level of exercise.
Vasospastic Angina: Amlodipine has been demonstrated to block constriction and restore blood flow in coronary arteries and arterioles in response to calcium, potassium epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro. This inhibition of coronary spasm is responsible for the effectiveness of amlodipine in vasospastic (Prinzmetal's or variant) angina.
Pharmacokinetics and Metabolism
After oral administration of therapeutic doses of amlodipine, absorption produces peak plasma concentrations between 6 and 12 hours. Absolute bioavailability has been estimated to be between 64 and 90%. The bioavailability of amlodipine is not altered by the presence of food. Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. Popclip 2019 1099 form. Ex vivo studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination half-life of about 30 to 50 hours. Steady-state plasma levels of amlodipine are reached after 7 to 8 days of consecutive daily dosing.
The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose. Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40 to 60%, and a lower initial dose may be required. A similar increase in AUC was observed in patients with moderate to severe heart failure.
Pediatric Patients
Sixty-two hypertensive patients aged 6 to 17 years received doses of amlodipine between 1.25 mg and 20 mg. Weight-adjusted clearance and volume of distribution were similar to values in adults.
Pharmacodynamics
Hemodynamics: Following administration of therapeutic doses to patients with hypertension, amlodipine produces vasodilation resulting in a reduction of supine and standing blood pressures. These decreases in blood pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels with chronic dosing. Although the acute intravenous administration of amlodipine decreases arterial blood pressure and increases heart rate in hemodynamic studies of patients with chronic stable angina, chronic oral administration of amlodipine in clinical trials did not lead to clinically significant changes in heart rate or blood pressures in normotensive patients with angina. With chronic once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hours. Plasma concentrations correlate with effect in both young and elderly patients. The magnitude of reduction in blood pressure with amlodipine is also correlated with the height of pretreatment elevation; thus, individuals with moderate hypertension (diastolic pressure 105 to 114 mmHg) had about a 50% greater response than patients with mild hypertension (diastolic pressure 90 to 104 mmHg). Normotensive subjects experienced no clinically significant change in blood pressures (+1/-2 mmHg). In hypertensive patients with normal renal function, therapeutic doses f amlodipine resulted in a decrease in renal vascular resistance and n increase in glomerular filtration rate and effective renal plasma flow without change in filtration fraction or proteinuria. As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with amlodipine have enerally demonstrated a small increase in cardiac index without significant influence on dP/dt or on left ventricular end diastolic pressure r volume. In hemodynamic studies, amlodipine has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and man, even when co-administered ith beta-blockers to man. Similar findings, however, have been observed in normals or well-compensated patients with heart failure with agents possessing significant negative inotropic effects.
Mechanism of Action
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. The precise mechanisms by which amlodipine relieves angina have not been fully delineated, but are thought to include the following:
Exertional Angina: In patients with exertional angina, amlodipine reduces the total peripheral resistance (afterload) against which the heart works and reduces the rate pressure product, and thus myocardial oxygen demand, at any given level of exercise.
Vasospastic Angina: Amlodipine has been demonstrated to block constriction and restore blood flow in coronary arteries and arterioles in response to calcium, potassium epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro. This inhibition of coronary spasm is responsible for the effectiveness of amlodipine in vasospastic (Prinzmetal's or variant) angina.
Pharmacokinetics and Metabolism
After oral administration of therapeutic doses of amlodipine, absorption produces peak plasma concentrations between 6 and 12 hours. Absolute bioavailability has been estimated to be between 64 and 90%. The bioavailability of amlodipine is not altered by the presence of food. Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. Popclip 2019 1099 form. Ex vivo studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination half-life of about 30 to 50 hours. Steady-state plasma levels of amlodipine are reached after 7 to 8 days of consecutive daily dosing.
The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose. Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40 to 60%, and a lower initial dose may be required. A similar increase in AUC was observed in patients with moderate to severe heart failure.
Pediatric Patients
Sixty-two hypertensive patients aged 6 to 17 years received doses of amlodipine between 1.25 mg and 20 mg. Weight-adjusted clearance and volume of distribution were similar to values in adults.
Pharmacodynamics
Hemodynamics: Following administration of therapeutic doses to patients with hypertension, amlodipine produces vasodilation resulting in a reduction of supine and standing blood pressures. These decreases in blood pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels with chronic dosing. Although the acute intravenous administration of amlodipine decreases arterial blood pressure and increases heart rate in hemodynamic studies of patients with chronic stable angina, chronic oral administration of amlodipine in clinical trials did not lead to clinically significant changes in heart rate or blood pressures in normotensive patients with angina. With chronic once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hours. Plasma concentrations correlate with effect in both young and elderly patients. The magnitude of reduction in blood pressure with amlodipine is also correlated with the height of pretreatment elevation; thus, individuals with moderate hypertension (diastolic pressure 105 to 114 mmHg) had about a 50% greater response than patients with mild hypertension (diastolic pressure 90 to 104 mmHg). Normotensive subjects experienced no clinically significant change in blood pressures (+1/-2 mmHg). In hypertensive patients with normal renal function, therapeutic doses f amlodipine resulted in a decrease in renal vascular resistance and n increase in glomerular filtration rate and effective renal plasma flow without change in filtration fraction or proteinuria. As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with amlodipine have enerally demonstrated a small increase in cardiac index without significant influence on dP/dt or on left ventricular end diastolic pressure r volume. In hemodynamic studies, amlodipine has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and man, even when co-administered ith beta-blockers to man. Similar findings, however, have been observed in normals or well-compensated patients with heart failure with agents possessing significant negative inotropic effects.
Jutoh 2 93 Pill Oval
Electrophysiologic Effects: Amlodipine does not change sinoatrial nodal function or atrioventricular conduction in intact animals or man. In patients with chronic stable angina, intravenous administration of 10 mg did not significantly alter A-H and H-V conduction and sinus node recovery time after pacing. Similar results were obtained in patients receiving amlodipine and concomitant beta-blockers. In clinical studies in which amlodipine was administered in combination with beta-blockers to patients with either hypertension or angina, no adverse effects on electrocardiographic parameters were observed. In clinical trials with angina patients alone, amlodipine therapy did not alter electrocardiographic intervals or produce higher degrees of AV blocks.
Clinical Studies
Effects in Hypertension: Adult Patients: The antihypertensive efficacy of amlodipine has been demonstrated in a total of 15 double-blind, placebo-controlled, randomized studies involving 800 patients on amlodipine and 538 on placebo. Once daily administration produced statistically significant placebo-corrected reductions in supine and standing blood pressures at 24 hours postdose, averaging about 12/6 mmHg in the standing position and 13/7 mmHg in the supine position in patients with mild to moderate hypertension. Maintenance of the blood pressure effect over the 24-hour dosing interval was observed, with little difference in peak and trough effect. Tolerance was not demonstrated in patients studied for up to 1 year. The 3 parallel, fixed dose, dose response studies showed that the reduction in supine and standing blood pressures was dose-related within the recommended dosing range. Effects on diastolic pressure were similar in young and older patients. The effect on systolic pressure was greater in older patients, perhaps because of greater baseline systolic pressure. Effects were similar in black patients and in white patients. Pediatric Patients: Two hundred sixty-eight hypertensive patients aged 6 to 17 years were randomized first to amlodipine 2.5 or 5 mg once daily for 4 weeks and then randomized again to the same dose or to placebo for another 4 weeks. Patients receiving 5 mg at the end of 8 weeks had lower blood pressure than those secondarily randomized to placebo. The magnitude of the treatment effect is difficult to interpret, but it is probably less than 5 mmHg systolic on the 5 mg dose. Adverse events were similar to those seen in adults.
Effects in Chronic Stable Angina: The effectiveness of 5 to 10 mg/day of amlodipine in exercise-induced angina has been evaluated in 8 placebo-controlled, double-blind clinical trials of up to 6 weeks duration involving 1038 patients (684 amlodipine, 354 placebo) with chronic stable angina. In 5 of the 8 studies significant increases in exercise time (bicycle or treadmill) were seen with the 10 mg dose. Increases in symptomlimited exercise time averaged 12.8% (63 sec) for amlodipine 10 mg, and averaged 7.9% (38 sec) for amlodipine 5 mg. Amlodipine 10 mg also increased time to 1 mm ST segment deviation in several studies and decreased angina attack rate. The sustained efficacy of amlodipine in angina patients has been demonstrated over long-term dosing. In patients with angina there were no clinically significant reductions in blood pressures (4/1 mmHg) or changes in heart rate (+0.3 bpm).
Jutoh 2 93 Pill 176
Effects in Vasospastic Angina: In a double-blind, placebo-controlled clinical trial of 4 weeks duration in 50 patients, amlodipine therapy decreased attacks by approximately 4/week compared with a placebo decrease of approximately 1/week (p<0.01). Two of 23 amlodipine and 7 of 27 placebo patients discontinued from the study due to lack of clinical improvement.
Studies in Patients with Congestive Heart Failure: Amlodipine besylate has been compared to placebo in four 8 to 12 week studies of patients with NYHA class II/III heart failure, involving a total of 697 patients. In these studies, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or left ventricular ejection fraction. In a long-term (follow-up at least 6 months, mean 13.8 months) placebo-controlled mortality/morbidity study of amlodipine besylate 5 to 10 mg in 1153 patients with NYHA classes III (N=931) or IV (N=222) heart failure on stable doses of diuretics, digoxin, and ACE inhibitors, amlodipine besylate had no effect on the primary endpoint of the study which was the combined endpoint of all-cause mortality and cardiac morbidity (as defined by lifethreatening arrhythmia, acute myocardial infarction, or hospitalization for worsened heart failure), or on NYHA classification, or symptoms of heart failure. Total combined all-cause mortality and cardiac morbidity events were 222/571 (39%) for patients on amlodipine besylate and 246/583 (42%) for patients on placebo; the cardiac morbid events represented about 25% of the endpoints in the study. Another study (PRAISE-2) randomized patients with NYHA class III (80%) or IV (20%) heart failure without clinical symptoms or objective evidence of underlying ischemic disease, on stable doses of ACE inhibitor (99%), digitalis (99%) and diuretics (99%), to placebo (N=827) or amlodipine besylate (N=827) and followed them for a mean of 33 months. There was no statistically significant difference between amlodipine besylate and placebo in the primary endpoint of all cause mortality (95% confidence limits from 8% reduction to 29% increase on amlodipine besylate). With amlodipine besylate there were more reports of pulmonary edema.
